The role of goblet cells and mucus in intestinal homeostasis.
Journal
Nature reviews. Gastroenterology & hepatology
ISSN: 1759-5053
Titre abrégé: Nat Rev Gastroenterol Hepatol
Pays: England
ID NLM: 101500079
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
accepted:
04
08
2022
pubmed:
13
9
2022
medline:
29
11
2022
entrez:
12
9
2022
Statut:
ppublish
Résumé
The intestinal tract faces numerous challenges that require several layers of defence. The tight epithelium forms a physical barrier that is further protected by a mucus layer, which provides various site-specific protective functions. Mucus is produced by goblet cells, and as a result of single-cell RNA sequencing identifying novel goblet cell subpopulations, our understanding of their various contributions to intestinal homeostasis has improved. Goblet cells not only produce mucus but also are intimately linked to the immune system. Mucus and goblet cell development is tightly regulated during early life and synchronized with microbial colonization. Dysregulation of the developing mucus systems and goblet cells has been associated with infectious and inflammatory conditions and predisposition to chronic disease later in life. Dysfunctional mucus and altered goblet cell profiles are associated with inflammatory conditions in which some mucus system impairments precede inflammation, indicating a role in pathogenesis. In this Review, we present an overview of the current understanding of the role of goblet cells and the mucus layer in maintaining intestinal health during steady-state and how alterations to these systems contribute to inflammatory and infectious disease.
Identifiants
pubmed: 36097076
doi: 10.1038/s41575-022-00675-x
pii: 10.1038/s41575-022-00675-x
doi:
Substances chimiques
Mucins
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
785-803Informations de copyright
© 2022. Springer Nature Limited.
Références
Boron, W. F. & Boulpaep, E. L. Medical physiology 3rd edn (Elsevier, 2017).
Johansson, M. E., Larsson, J. M. & Hansson, G. C. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc. Natl Acad. Sci. USA 108, 4659–4665 (2011).
pubmed: 20615996
Lechuga, S. & Ivanov, A. I. Disruption of the epithelial barrier during intestinal inflammation: quest for new molecules and mechanisms. Biochim. Biophys. Acta Mol. Cell Res. 1864, 1183–1194 (2017).
pubmed: 28322932
Atuma, C., Strugula, V., Allen, A. & Holm, L. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G922–G929 (2001).
pubmed: 11292601
Ermund, A., Schutte, A., Johansson, M. E., Gustafsson, J. K. & Hansson, G. C. Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer’s patches. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G341–G347 (2013).
pubmed: 23832518
pmcid: 3761247
Mestecky, J. et al. Mucosal Immunology (Academic, 2015).
Birchenough, G. M., Nyström, E. E., Johansson, M. E. & Hansson, G. C. A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science 352, 1535–1542 (2016).
pubmed: 27339979
pmcid: 5148821
Grondin, J. A., Kwon, Y. H., Far, P. M., Haq, S. & Khan, W. I. Mucins in intestinal mucosal defense and inflammation: learning from clinical and experimental studies. Front. Immunol. https://doi.org/10.3389/fimmu.2020.02054 (2020).
doi: 10.3389/fimmu.2020.02054
pubmed: 33013869
pmcid: 7500085
Knoop, K. A. et al. Synchronization of mothers and offspring promotes tolerance and limits allergy. JCI Insight https://doi.org/10.1172/jci.insight.137943 (2020).
doi: 10.1172/jci.insight.137943
pubmed: 32759496
pmcid: 7455068
Bergstrom, K. et al. Proximal colon-derived O-glycosylated mucus encapsulates and modulates the microbiota. Science 370, 467–472 (2020).
pubmed: 33093110
pmcid: 8132455
Kulkarni, D. H. et al. Goblet cell associated antigen passages support the induction and maintenance of oral tolerance. Mucosal Immunol. 13, 271–282 (2020).
pubmed: 31819172
Witten, J., Samad, T. & Ribbeck, K. Selective permeability of mucus barriers. Curr. Opin. Biotechnol. 52, 124–133 (2018).
pubmed: 29674157
pmcid: 7132988
Rodriguez-Pineiro, A. M. et al. Studies of mucus in mouse stomach, small intestine, and colon. II. Gastrointestinal mucus proteome reveals Muc2 and Muc5ac accompanied by a set of core proteins. Am. J. Physiol. Gastrointest. Liver Physiol. 305, G348–G356 (2013).
pubmed: 23832517
pmcid: 3761249
van der Post, S. et al. Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut 68, 2142–2151 (2019).
pubmed: 30914450
Nyström, E. E. L. et al. Calcium-activated chloride channel regulator 1 (CLCA1) controls mucus expansion in colon by proteolytic activity. EBioMedicine 33, 134–143 (2018).
pubmed: 29885864
pmcid: 6085540
Ehrencrona, E. et al. The IgG Fc-binding protein FCGBP is secreted with all GDPH sequences cleaved, but maintained by inter-fragment disulfide bonds. J. Biol. Chem. https://doi.org/10.1016/j.jbc.2021.100871 (2021).
doi: 10.1016/j.jbc.2021.100871
pubmed: 34126068
pmcid: 8267560
Jabbar, K. S. et al. Association between Brachyspira and irritable bowel syndrome with diarrhoea. Gut 70, 1117–1129 (2021).
pubmed: 33177165
Ambort, D. et al. Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.1120269109 (2012).
doi: 10.1073/pnas.1120269109
pubmed: 22451922
pmcid: 3497767
Javitt, G. et al. Assembly mechanism of mucin and von Willebrand factor polymers. Cell 183, 717–729.e6 (2020).
pubmed: 33031746
pmcid: 7599080
Recktenwald, C. V. & Hansson, G. C. The reduction-insensitive bonds of the MUC2 mucin are isopeptide bonds. J. Biol. Chem. 291, 13580–13590 (2016).
pubmed: 27129250
pmcid: 4919444
Arike, L., Hansson, G. C. & Recktenwald, C. V. Identifying transglutaminase reaction products via mass spectrometry as exemplified by the MUC2 mucin – pitfalls and traps. Anal. Biochem. 597, 113668 (2020).
pubmed: 32222540
pmcid: 7184670
Birchenough, G. M., Johansson, M. E., Gustafsson, J. K., Bergstrom, J. H. & Hansson, G. C. New developments in goblet cell mucus secretion and function. Mucosal Immunol. 8, 712–719 (2015).
pubmed: 25872481
pmcid: 4631840
Javitt, G. et al. Intestinal Gel-forming mucins polymerize by disulfide-mediated dimerization of D3 domains. J. Mol. Biol. 431, 3740–3752 (2019).
pubmed: 31310764
pmcid: 6739602
Neutra, M. R., O’Malley, L. J. & Specian, R. D. Regulation of intestinal goblet cell secretion. II. A survey of potential secretagogues. Am. J. Physiol. 242, G380–G387 (1982).
pubmed: 7065260
Gustafsson, J. K. et al. Carbachol-induced colonic mucus formation requires transport via NKCC1, K(+) channels and CFTR. Pflugers Arch. 467, 1403–1415 (2015).
pubmed: 25139191
Schutte, A. et al. Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus. Proc. Natl Acad. Sci. USA 111, 12396–12401 (2014).
pubmed: 25114233
pmcid: 4151749
Smithson, K. W., Millar, D. B., Jacobs, L. R. & Gray, G. M. Intestinal diffusion barrier: unstirred water layer or membrane surface mucous coat? Science 214, 1241–1244 (1981).
pubmed: 7302593
Lai, S. K., Wang, Y.-Y., Wirtz, D. & Hanes, J. Micro- and macrorheology of mucus. Adv. Drug Deliv. Rev. 61, 86–100 (2009).
pubmed: 19166889
pmcid: 2736374
Critchfield, A. S. et al. Cervical mucus properties stratify risk for preterm birth. PLoS ONE 8, e69528 (2013).
pubmed: 23936335
pmcid: 3731331
Krupa, L. et al. Comparing the permeability of human and porcine small intestinal mucus for particle transport studies. Sci. Rep. 10, 20290 (2020).
pubmed: 33219331
pmcid: 7679454
Witten, J. & Ribbeck, K. The particle in the spider’s web: transport through biological hydrogels. Nanoscale 9, 8080–8095 (2017).
pubmed: 28580973
pmcid: 5841163
Johansson, M. E. et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl Acad. Sci. USA 105, 15064–15069 (2008).
pubmed: 18806221
pmcid: 2567493
Kamphuis, J. B. J., Mercier-Bonin, M., Eutamene, H. & Theodorou, V. Mucus organisation is shaped by colonic content; a new view. Sci. Rep. 7, 8527 (2017).
pubmed: 28819121
pmcid: 5561085
Schneider, H., Pelaseyed, T., Svensson, F. & Johansson, M. E. V. Study of mucin turnover in the small intestine by in vivo labeling. Sci. Rep. 8, 5760 (2018).
pubmed: 29636525
pmcid: 5893601
Johansson, M. E. Fast renewal of the distal colonic mucus layers by the surface goblet cells as measured by in vivo labeling of mucin glycoproteins. PLoS ONE 7, e41009 (2012).
pubmed: 22815896
pmcid: 3398881
Arike, L. et al. Protein turnover in epithelial cells and mucus along the gastrointestinal tract is coordinated by the spatial location and microbiota. Cell Rep. 30, 1077–1087.e3 (2020).
pubmed: 31995731
pmcid: 6996021
Macierzanka, A., Mackie, A. R. & Krupa, L. Permeability of the small intestinal mucus for physiologically relevant studies: impact of mucus location and ex vivo treatment. Sci. Rep. 9, 17516 (2019).
pubmed: 31772308
pmcid: 6879640
Schroeder, B. O. et al. Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice. J. Biol. Chem. 295, 15712–15726 (2020).
pubmed: 32900852
pmcid: 7667970
Sababi, M., Nilsson, E. & Holm, L. Mucus and alkali secretion in the rat duodenum: effects of indomethacin, Nω-nitro-L-arginine, and luminal acid. Gastroenterology 109, 1526–1534 (1995).
pubmed: 7557135
McQueen, S., Hutton, D., Allen, A. & Garner, A. Gastric and duodenal surface mucus gel thickness in rat: effects of prostaglandins and damaging agents. Am. J. Physiol. 245, G388–G393 (1983).
pubmed: 6614182
Sotres, J., Jankovskaja, S., Wannerberger, K. & Arnebrant, T. Ex-vivo force spectroscopy of intestinal mucosa reveals the mechanical properties of mucus blankets. Sci. Rep. 7, 7270 (2017).
pubmed: 28779181
pmcid: 5544714
Johansson, M. E. et al. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut 63, 281–291 (2014).
pubmed: 23426893
Gustafsson, J. K. et al. Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype. J. Exp. Med. 209, 1263–1272 (2012).
pubmed: 22711878
pmcid: 3405509
Allen, A. & Flemstrom, G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am. J. Physiol. Cell Physiol. 288, C1–C19 (2005).
pubmed: 15591243
Bell, A. E. et al. Properties of gastric and duodenal mucus: effect of proteolysis, disulfide reduction, bile, acid, ethanol, and hypertonicity on mucus gel structure. Gastroenterology 88, 269–280 (1985).
pubmed: 3917263
Johansson, M. E. et al. Normalization of host intestinal mucus layers requires long-term microbial colonization. Cell Host Microbe 18, 582–592 (2015).
pubmed: 26526499
pmcid: 4648652
Schroeder, B. O. et al. Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell Host Microbe 23, 27–40.e7 (2018).
pubmed: 29276171
Petersson, J. et al. Importance and regulation of the colonic mucus barrier in a mouse model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 300, G327–G333 (2011).
pubmed: 21109593
Mukherjee, S. & Hooper, L. V. Antimicrobial defense of the intestine. Immunity 42, 28–39 (2015).
pubmed: 25607457
Bevins, C. L. & Salzman, N. H. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat. Rev. Microbiol. 9, 356–368 (2011).
pubmed: 21423246
Macpherson, A. J. & McCoy, K. D. Stratification and compartmentalisation of immunoglobulin responses to commensal intestinal microbes. Semin. Immunol. 25, 358–363 (2013).
pubmed: 24238818
Meyer-Hoffert, U. et al. Secreted enteric antimicrobial activity localises to the mucus surface layer. Gut 57, 764–771 (2008).
pubmed: 18250125
Gustafsson, J. K. et al. An ex vivo method for studying mucus formation, properties, and thickness in human colonic biopsies and mouse small and large intestinal explants. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G430–G438 (2012).
pubmed: 22159279
Nava, G. M., Friedrichsen, H. J. & Stappenbeck, T. S. Spatial organization of intestinal microbiota in the mouse ascending colon. ISME J. 5, 627–638 (2011).
pubmed: 20981114
Hugenholtz, F. & de Vos, W. M. Mouse models for human intestinal microbiota research: a critical evaluation. Cell Mol. Life Sci. 75, 149–160 (2018).
pubmed: 29124307
Swidsinski, A., Loening-Baucke, V., Verstraelen, H., Osowska, S. & Doerffel, Y. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterology 135, 568–579 (2008).
pubmed: 18570896
Nyström, E. E. L. et al. An intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function. Science 372, eabb1590 (2021).
pubmed: 33859001
pmcid: 8542866
Burclaff, J. et al. A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics. Cell. Mol. Gastroenterol. Hepatol. https://doi.org/10.1016/j.jcmgh.2022.02.007 (2022).
doi: 10.1016/j.jcmgh.2022.02.007
pubmed: 35176508
pmcid: 9043569
Bergstrom, J. H. et al. Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16. Proc. Natl Acad. Sci. USA 113, 13833–13838 (2016).
pubmed: 27849619
pmcid: 5137749
Luis, A. S. et al. A single sulfatase is required to access colonic mucin by a gut bacterium. Nature 598, 332–337 (2021).
pubmed: 34616040
pmcid: 9128668
Martens, E. C., Chiang, H. C. & Gordon, J. I. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 4, 447–457 (2008).
pubmed: 18996345
pmcid: 2605320
Desai, M. S. et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 1339–1353.e21 (2016).
pubmed: 27863247
pmcid: 5131798
Zou, J. et al. Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host Microbe 23, 41–53.e4 (2018).
pubmed: 29276170
Birchenough, G. M. et al. Postnatal development of the small intestinal mucosa drives age-dependent, regio-selective susceptibility to Escherichia coli K1 infection. Sci. Rep. 7, 83 (2017).
pubmed: 28250440
pmcid: 5427930
Burger-van Paassen, N. et al. Colitis development during the suckling-weaning transition in mucin Muc2-deficient mice. Am. J. Physiol. Gastrointest. Liver Physiol. 301, G667–G678 (2011).
pubmed: 21700902
Fu, J. et al. Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice. J. Clin. Invest. 121, 1657–1666 (2011).
pubmed: 21383503
pmcid: 3069788
Van der Sluis, M. et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131, 117–129 (2006).
pubmed: 16831596
Velcich, A. et al. Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295, 1726–1729 (2002).
pubmed: 11872843
Barker, N., Van de, W. M. & Clevers, H. The intestinal stem cell. Genes Dev. 22, 1856–1864 (2008).
pubmed: 18628392
pmcid: 2735277
Noah, T. K., Donahue, B. & Shroyer, N. F. Intestinal development and differentiation. Exp. Cell Res. 317, 2702–2710 (2011).
pubmed: 21978911
pmcid: 3210330
Koo, B.-K., van Es Johan, H., van den Born, M. & Clevers, H. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia. Proc. Natl Acad. Sci. USA 112, 7548–7550 (2015).
pubmed: 26023187
pmcid: 4475934
Lo, Y. H. et al. Transcriptional regulation by ATOH1 and its target SPDEF in the intestine. Cell. Mol. Gastroenterol. Hepatol. 3, 51–71 (2017).
pubmed: 28174757
Noah, T. K., Kazanjian, A., Whitsett, J. & Shroyer, N. F. SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells. Exp. Cell Res. 316, 452–465 (2010).
pubmed: 19786015
Shroyer, N. F. et al. Intestine-specific ablation of mouse atonal homolog 1 (Math1) reveals a role in cellular homeostasis. Gastroenterology 132, 2478–2488 (2007).
pubmed: 17570220
Shroyer, N. F., Wallis, D., Venken, K. J. T., Bellen, H. J. & Zoghbi, H. Y. Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation. Genes Dev. 19, 2412–2417 (2005).
pubmed: 16230531
pmcid: 1257395
Gregorieff, A. et al. The Ets-domain transcription factor Spdef promotes maturation of goblet and Paneth cells in the intestinal epithelium. Gastroenterology 137, 1333–1345 (2009).
pubmed: 19549527
Wang, Y. et al. Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine. J. Exp. Med. https://doi.org/10.1084/jem.20191130 (2020).
doi: 10.1084/jem.20191130
pubmed: 32936886
pmcid: 7769166
Barker, N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat. Rev. Mol. Cell Biol. 15, 19–33 (2014).
pubmed: 24326621
Dalerba, P. et al. Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat. Biotechnol. 29, 1120–1127 (2011).
pubmed: 22081019
pmcid: 3237928
Tabula Muris, C. et al. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature 562, 367–372 (2018).
Haber, A. L. et al. A single-cell survey of the small intestinal epithelium. Nature 551, 333–339 (2017).
pubmed: 29144463
pmcid: 6022292
Herring, C. A. et al. Unsupervised trajectory analysis of single-cell RNA-Seq and imaging data reveals alternative tuft cell origins in the gut. Cell Syst. 6, 37–51.e9 (2018).
pubmed: 29153838
Moor, A. E. et al. Spatial reconstruction of single enterocytes uncovers broad zonation along the intestinal villus axis. Cell 175, 1156–1167.e15 (2018).
pubmed: 30270040
Parikh, K. et al. Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature 567, 49–55 (2019).
pubmed: 30814735
Smillie, C. S. et al. Intra- and inter-cellular rewiring of the human colon during ulcerative colitis. Cell 178, 714–730.e22 (2019).
pubmed: 31348891
pmcid: 6662628
Capdevila, C. et al. Cellular origins and lineage relationships of the intestinal epithelium. Am. J. Physiol. Gastrointest. Liver Physiol. 321, G413–G425 (2021).
pubmed: 34431400
pmcid: 8560372
Mills, J. C., Stanger, B. Z. & Sander, M. Nomenclature for cellular plasticity: are the terms as plastic as the cells themselves? EMBO J. 38, e103148 (2019).
pubmed: 31475380
pmcid: 6769377
Larsen, H. L. & Jensen, K. B. Reprogramming cellular identity during intestinal regeneration. Curr. Opin. Genet. Dev. 70, 40–47 (2021).
pubmed: 34062491
Radwan, K. A., Oliver, M. G. & Specian, R. D. Cytoarchitectural reorganization of rabbit colonic goblet cells during baseline secretion. Am. J. Anat. 189, 365–376 (1990).
pubmed: 2285043
Rothenberg, M. E. et al. Identification of a cKit(+) colonic crypt base secretory cell that supports Lgr5(+) stem cells in mice. Gastroenterology 142, 1195–1205.e6 (2012).
pubmed: 22333952
Specian, R. D. & Neutra, M. R. Mechanism of rapid mucus secretion in goblet cells stimulated by acetylcholine. J. Cell Biol. 85, 626–640 (1980).
pubmed: 7391135
Jaramillo, A. M. et al. Different Munc18 proteins mediate baseline and stimulated airway mucin secretion. JCI Insight https://doi.org/10.1172/jci.insight.124815 (2019).
doi: 10.1172/jci.insight.124815
pubmed: 30721150
pmcid: 6483006
Cornick, S., Kumar, M., Moreau, F., Gaisano, H. & Chadee, K. VAMP8-mediated MUC2 mucin exocytosis from colonic goblet cells maintains innate intestinal homeostasis. Nat. Commun. 10, 4306 (2019).
pubmed: 31541089
pmcid: 6754373
Huang, B. et al. Mucosal profiling of pediatric-onset colitis and IBD reveals common pathogenics and therapeutic pathways. Cell 179, 1160–1176.e24 (2019).
pubmed: 31730855
Halm, D. R. & Halm, S. T. Secretagogue response of goblet cells and columnar cells in human colonic crypts. Am. J. Physiol. Cell Physiol. 278, C212–C233 (2000).
pubmed: 10644530
Garcia, M. A., Yang, N. & Quinton, P. M. Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. J. Clin. Invest. 119, 2613–2622 (2009).
pubmed: 19726884
pmcid: 2735925
Phillips, T. E. Both crypt and villus intestinal goblet cells secrete mucin in response to cholinergic stimulation. Am. J. Physiol. 262, G327–G331 (1992).
pubmed: 1539664
Corfield, A. P. Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim. Biophys. Acta Gen. Subj. 1850, 236–252 (2015).
Harada, N. et al. Human IgGFc binding protein (FcγBP) in colonic epithelial cells exhibits mucin-like structure. J. Biol. Chem. 272, 15232–15241 (1997).
pubmed: 9182547
Tsuru, A. et al. Negative feedback by IRE1β optimizes mucin production in goblet cells. Proc. Natl Acad. Sci. USA 110, 2864–2869 (2013).
pubmed: 23386727
pmcid: 3581977
Park, S. W. et al. The protein disulfide isomerase AGR2 is essential for production of intestinal mucus. Proc. Natl Acad. Sci. USA 106, 6950–6955 (2009).
pubmed: 19359471
pmcid: 2678445
Zhao, F. et al. Disruption of Paneth and goblet cell homeostasis and increased endoplasmic reticulum stress in Agr2-/- mice. Dev. Biol. 338, 268–277 (2010).
Zheng, W. et al. Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease. Genes Immun. 7, 11–18 (2006).
pubmed: 16222343
Cloots, E. et al. Evolution and function of the epithelial cell-specific ER stress sensor IRE1β. Mucosal Immunol. 14, 1235–1246 (2021).
pubmed: 34075183
pmcid: 8528705
Heazlewood, C. K. et al. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med. 5, e54 (2008).
pubmed: 18318598
pmcid: 2270292
McGuckin, M. A., Eri, R. D., Das, I., Lourie, R. & Florin, T. H. ER stress and the unfolded protein response in intestinal inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 298, G820–G832 (2010).
pubmed: 20338921
Litvak, Y., Byndloss, M. X. & Baumler, A. J. Colonocyte metabolism shapes the gut microbiota. Science https://doi.org/10.1126/science.aat9076 (2018).
doi: 10.1126/science.aat9076
pubmed: 30498100
pmcid: 6296223
Montgomery, R. K., Mulberg, A. E. & Grand, R. J. Development of the human gastrointestinal tract: twenty years of progress. Gastroenterology 116, 702–731 (1999).
pubmed: 10029630
Stanford, A. H. et al. A direct comparison of mouse and human intestinal development using epithelial gene expression patterns. Pediatr. Res. 88, 66–76 (2020).
pubmed: 31242501
Gomes, J. R. et al. Goblet cells and intestinal alkaline phosphatase expression (IAP) during the development of the rat small intestine. Acta Histochem. 119, 71–77 (2017).
pubmed: 27939968
Lev, R., Siegel, H. I. & Bartman, J. Histochemical studies of developing human fetal small intestine. Histochemie 29, 103–119 (1972).
pubmed: 4260029
Elmentaite, R. et al. Single-cell sequencing of developing human gut reveals transcriptional links to childhood Crohn’s disease. Dev. Cell 55, 771–783.e5 (2020).
pubmed: 33290721
pmcid: 7762816
Buisine, M. P. et al. Mucin gene expression in human embryonic and fetal intestine. Gut 43, 519–524 (1998).
pubmed: 9824580
pmcid: 1727278
Chambers, J. A., Hollingsworth, M. A., Trezise, A. E. & Harris, A. Developmental expression of mucin genes MUC1 and MUC2. J. Cell Sci. 107, 413–424 (1994).
pubmed: 7515892
Fawkner-Corbett, D. et al. Spatiotemporal analysis of human intestinal development at single-cell resolution. Cell 184, 810–826.e23 (2021).
pubmed: 33406409
pmcid: 7864098
Gao, S. et al. Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing. Nat. Cell Biol. 20, 721–734 (2018).
pubmed: 29802404
Colony, P. C. & Specian, R. D. Endocytosis and vesicular traffic in fetal and adult colonic goblet cells. Anat. Rec. 218, 365–372 (1987).
pubmed: 3662039
Colony, P. C. & Neutra, M. R. Epithelial differentiation in the fetal rat colon. I. Plasma membrane phosphatase activities. Dev. Biol. 97, 349–363 (1983).
pubmed: 6303878
Mathan, M., Moxey, P. C. & Trier, J. S. Morphogenesis of fetal rat duodenal villi. Am. J. Anat. 146, 73–92 (1976).
pubmed: 937208
Sumigray, K. D., Terwilliger, M. & Lechler, T. Morphogenesis and compartmentalization of the intestinal crypt. Dev. Cell 45, 183–197.e5 (2018).
pubmed: 29689194
pmcid: 5987226
Arévalo Sureda, E., Weström, B., Pierzynowski, S. G. & Prykhodko, O. Maturation of the intestinal epithelial barrier in neonatal rats coincides with decreased FcRn expression, replacement of vacuolated enterocytes and changed Blimp-1 expression. PLoS ONE 11, e0164775 (2016).
pubmed: 27736989
pmcid: 5063338
Skrzypek, T. et al. The contribution of vacuolated foetal-type enterocytes in the process of maturation of the small intestine in piglets. J. Anim. Feed. Sci. 27, 187–201 (2018).
Clark, S. L. Jr. The ingestion of proteins and colloidal materials by columnar absorptive cells of the small intestine in suckling rats and mice. J. Biophys. Biochem. Cytol. 5, 41–50 (1959).
pubmed: 13630932
pmcid: 2224611
Reisinger, K. W. et al. Intestinal fatty acid-binding protein: a possible marker for gut maturation. Pediatr. Res. 76, 261–268 (2014).
pubmed: 24956227
Israel, E. J., Simister, N., Freiberg, E., Caplan, A. & Walker, W. A. Immunoglobulin G binding sites on the human foetal intestine: a possible mechanism for the passive transfer of immunity from mother to infant. Immunology 79, 77–81 (1993).
pubmed: 8509144
pmcid: 1422058
Malmuthuge, N. & Griebel, P. J. Fetal environment and fetal intestine are sterile during the third trimester of pregnancy. Vet. Immunol. Immunopathol. 204, 59–64 (2018).
pubmed: 30290960
Perez-Munoz, M. E., Arrieta, M. C., Ramer-Tait, A. E. & Walter, J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 5, 48 (2017).
pubmed: 28454555
pmcid: 5410102
Urushiyama, D. et al. Microbiome profile of the amniotic fluid as a predictive biomarker of perinatal outcome. Sci. Rep. 7, 12171 (2017).
pubmed: 28939908
pmcid: 5610236
Wang, L. X. et al. Epidermal growth factor promotes intestinal secretory cell differentiation in weaning piglets via Wnt/β-catenin signalling. Animal 14, 790–798 (2020).
pubmed: 31650938
Bergström, A. et al. Nature of bacterial colonization influences transcription of mucin genes in mice during the first week of life. BMC Res. Notes 5, 402 (2012).
pubmed: 22857743
pmcid: 3465226
Fança-Berthon, P. et al. Intrauterine growth restriction alters postnatal colonic barrier maturation in rats. Pediatr. Res. 66, 47–52 (2009).
pubmed: 19287349
McDole, J. R. et al. Goblet cells deliver luminal antigen to CD103
pubmed: 22422267
pmcid: 3313460
Hansen, G. H., Rasmussen, K., Niels-Christiansen, L. L. & Danielsen, E. M. Endocytic trafficking from the small intestinal brush border probed with FM dye. Am. J. Physiol. Gastrointest. Liver Physiol. 297, G708–G715 (2009).
pubmed: 19679822
Knoop, K. A., McDonald, K. G., McCrate, S., McDole, J. R. & Newberry, R. D. Microbial sensing by goblet cells controls immune surveillance of luminal antigens in the colon. Mucosal Immunol. 8, 198–210 (2015).
pubmed: 25005358
Noah, T. K. et al. IL-13-induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis. J. Allergy Clin. Immunol. 144, 1058–1073.e3 (2019).
pubmed: 31175877
pmcid: 6779525
Gustafsson, J. K. et al. Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis. eLife 10, e67292 (2021).
pubmed: 34677124
pmcid: 8594945
Knoop, K. A. et al. Antibiotics promote the sampling of luminal antigens and bacteria via colonic goblet cell associated antigen passages. Gut Microbes 8, 400–411 (2017).
pubmed: 28267403
pmcid: 5570560
Knoop, K. A. et al. Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria. Sci. Immunol. 2, eaao1314 (2017).
pubmed: 29246946
pmcid: 5759965
Al Nabhani, Z. et al. A weaning reaction to microbiota is required for resistance to immunopathologies in the adult. Immunity 50, 1276–1288.e5 (2019).
pubmed: 30902637
Shan, M. et al. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 342, 447–453 (2013).
pubmed: 24072822
pmcid: 4005805
Barrios, B. E., Maccio-Maretto, L., Nazar, F. N. & Correa, S. G. A selective window after the food-intake period favors tolerance induction in mesenteric lymph nodes. Mucosal Immunol. 12, 108–116 (2019).
pubmed: 30327533
Barbosa, F. L. et al. Goblet cells contribute to ocular surface immune tolerance-implications for dry eye disease. Int. J. Mol. Sci. https://doi.org/10.3390/ijms18050978 (2017).
doi: 10.3390/ijms18050978
pubmed: 29156553
pmcid: 5713357
Ko, B. Y., Xiao, Y., Barbosa, F. L., de Paiva, C. S. & Pflugfelder, S. C. Goblet cell loss abrogates ocular surface immune tolerance. JCI Insight https://doi.org/10.1172/jci.insight.98222 (2018).
doi: 10.1172/jci.insight.98222
pubmed: 29415888
pmcid: 5821180
Kulkarni, D. H. et al. Goblet cell associated antigen passages are inhibited during Salmonella typhimurium infection to prevent pathogen dissemination and limit responses to dietary antigens. Mucosal Immunol. 11, 1103–1113 (2018).
pubmed: 29445136
pmcid: 6037413
Wlodarska, M. et al. NLRP6 inflammasome orchestrates the colonic host–microbial interface by regulating goblet cell mucus secretion. Cell 156, 1045–1059 (2014).
pubmed: 24581500
pmcid: 4017640
Volk, J. K. et al. The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function. J. Exp. Med. 216, 2602–2618 (2019).
pubmed: 31420376
pmcid: 6829596
Grootjans, J. et al. Ischaemia-induced mucus barrier loss and bacterial penetration are rapidly counteracted by increased goblet cell secretory activity in human and rat colon. Gut 62, 250–258 (2013).
pubmed: 22637697
Grootjans, J., Hundscheid, I. H. & Buurman, W. A. Goblet cell compound exocytosis in the defense against bacterial invasion in the colon exposed to ischemia–reperfusion. Gut Microbes 4, 232–235 (2013).
pubmed: 23542685
pmcid: 3669168
Johansson, M. E. & Hansson, G. C. The goblet cell: a key player in ischaemia–reperfusion injury. Gut 62, 188–189 (2013).
pubmed: 22689515
Sovran, B. et al. Age-associated impairment of the mucus barrier function is associated with profound changes in microbiota and immunity. Sci. Rep. 9, 1437 (2019).
pubmed: 30723224
pmcid: 6363726
Hansen, A. K., Hansen, C. H., Krych, L. & Nielsen, D. S. Impact of the gut microbiota on rodent models of human disease. World J. Gastroenterol. 20, 17727–17736 (2014).
pubmed: 25548471
pmcid: 4273123
Johansson, M. E. et al. Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model. PLoS ONE 5, e12238 (2010).
pubmed: 20805871
pmcid: 2923597
Liu, J. Z. & Anderson, C. A. Genetic studies of Crohn’s disease: past, present and future. Best. Pract. Res. Clin. Gastroenterol. 28, 373–386 (2014).
pubmed: 24913378
pmcid: 4075408
Adolph, T. E. et al. Paneth cells as a site of origin for intestinal inflammation. Nature 503, 272–276 (2013).
pubmed: 24089213
pmcid: 3862182
Wehkamp, J. & Stange, E. F. An update review on the Paneth cell as key to ileal Crohn’s disease. Front. Immunol. 11, 646 (2020).
pubmed: 32351509
pmcid: 7174711
Kaser, A. et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134, 743–756 (2008).
pubmed: 18775308
pmcid: 2586148
Lassen, K. G. et al. Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense. Proc. Natl Acad. Sci. USA 111, 7741–7746 (2014).
pubmed: 24821797
pmcid: 4040621
Pullan, R. D. Colonic mucus, smoking and ulcerative colitis. Ann. R. Coll. Surg. Engl. 78, 85–91 (1996).
pubmed: 8678464
pmcid: 2502541
Pullan, R. D. et al. Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis. Gut 35, 353–359 (1994).
pubmed: 8150346
pmcid: 1374589
Nonnecke, E. B. et al. Human intelectin-1 (ITLN1) genetic variation and intestinal expression. Sci. Rep. 11, 12889 (2021).
pubmed: 34145348
pmcid: 8213764
Strugala, V., Dettmar, P. W. & Pearson, J. P. Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn’s disease. Int. J. Clin. Pract. 62, 762–769 (2008).
pubmed: 18194279
Gersemann, M. et al. Differences in goblet cell differentiation between Crohn’s disease and ulcerative colitis. Differentiation 77, 84–94 (2009).
pubmed: 19281767
Coleman, O. I. & Haller, D. ER stress and the UPR in shaping intestinal tissue homeostasis and immunity. Front. Immunol. https://doi.org/10.3389/fimmu.2019.02825 (2019).
doi: 10.3389/fimmu.2019.02825
pubmed: 31867005
pmcid: 6904315
Tawiah, A. et al. High MUC2 mucin biosynthesis in goblet cells impedes restitution and wound healing by elevating endoplasmic reticulum stress and altered production of growth factors. Am. J. Pathol. 188, 2025–2041 (2018).
pubmed: 29935164
Wilson, R. et al. Identification of key pro-survival proteins in isolated colonic goblet cells of Winnie, a murine model of spontaneous colitis. Inflamm. Bowel Dis. 26, 80–92 (2020).
pubmed: 31504521
Wang, R. et al. Gut microbiota shape the inflammatory response in mice with an epithelial defect. Gut Microbes 13, 1887720 (2021).
pmcid: 7928202
Das, I. et al. Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins. J. Exp. Med. 210, 1201–1216 (2013).
pubmed: 23650437
pmcid: 3674691
Larsson, J. M. et al. Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation. Inflamm. Bowel Dis. 17, 2299–2307 (2011).
pubmed: 21290483
Tytgat, K. M., van der Wal, J. W., Einerhand, A. W., Buller, H. A. & Dekker, J. Quantitative analysis of MUC2 synthesis in ulcerative colitis. Biochem. Biophys. Res. Commun. 224, 397–405 (1996).
pubmed: 8702401
Xiao, F. et al. Slc26a3 deficiency is associated with loss of colonic HCO secretion, absence of a firm mucus layer and barrier impairment in mice. Acta Physiol. https://doi.org/10.1111/apha.12220 (2013).
doi: 10.1111/apha.12220
Gurney, M. A., Laubitz, D., Ghishan, F. K. & Kiela, P. R. Pathophysiology of Intestinal Na
pubmed: 28090568
Sellon, R. K. et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224–5231 (1998).
pubmed: 9784526
pmcid: 108652
Rigottier-Gois, L. Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis. ISME J. 7, 1256–1261 (2013).
pubmed: 23677008
pmcid: 3695303
Guo, X. Y., Liu, X. J. & Hao, J. Y. Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment. J. Dig. Dis. 21, 147–159 (2020).
pubmed: 32040250
Jakobsson, H. E. et al. The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep. 16, 164–177 (2015).
pubmed: 25525071
Miyauchi, E. et al. Analysis of colonic mucosa-associated microbiota using endoscopically collected lavage. Sci. Rep. 12, 1758 (2022).
pubmed: 35110685
pmcid: 8810796
Li, H. et al. The outer mucus layer hosts a distinct intestinal microbial niche. Nat. Commun. 6, 8292 (2015).
pubmed: 26392213
Lavelle, A. et al. Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers. Gut 64, 1553–1561 (2015).
pubmed: 25596182
Sunderhauf, A. et al. Loss of mucosal p32/gC1qR/HABP1 triggers energy deficiency and impairs goblet cell differentiation in ulcerative colitis. Cell. Mol. Gastroenterol. Hepatol. 12, 229–250 (2021).
pubmed: 33515804
pmcid: 8135049
Kumar, M. et al. Increased intestinal permeability exacerbates sepsis through reduced hepatic SCD-1 activity and dysregulated iron recycling. Nat. Commun. 11, 483 (2020).
pubmed: 31980623
pmcid: 6981269
Ozdirik, B., Muller, T., Wree, A., Tacke, F. & Sigal, M. The role of microbiota in primary sclerosing cholangitis and related biliary malignancies. Int. J. Mol. Sci. https://doi.org/10.3390/ijms22136975 (2021).
doi: 10.3390/ijms22136975
pubmed: 34445276
pmcid: 8395312
Fenton, C. G., Taman, H., Florholmen, J., Sorbye, S. W. & Paulssen, R. H. Transcriptional signatures that define ulcerative colitis in remission. Inflamm. Bowel Dis. 27, 94–105 (2021).
pubmed: 32322884
Bergstrom, K. S. et al. Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa. PLoS. Pathog. 6, e1000902 (2010).
pubmed: 20485566
pmcid: 2869315
Sharpe, C., Thornton, D. J. & Grencis, R. K. A sticky end for gastrointestinal helminths; the role of the mucus barrier. Parasite Immunol. 40, e12517 (2018).
pubmed: 29355990
pmcid: 5900928
Hasnain, S. Z., Gallagher, A. L., Grencis, R. K. & Thornton, D. J. A new role for mucins in immunity: insights from gastrointestinal nematode infection. Int. J. Biochem. Cell Biol. 45, 364–374 (2013).
pubmed: 23107603
Allain, T., Amat, C. B., Motta, J. P., Manko, A. & Buret, A. G. Interactions of Giardia sp. with the intestinal barrier: epithelium, mucus, and microbiota. Tissue Barriers 5, e1274354 (2017).
pubmed: 28452685
pmcid: 5362998
Furter, M., Sellin, M. E., Hansson, G. C. & Hardt, W. D. Mucus architecture and near-surface swimming affect distinct Salmonella typhimurium infection patterns along the murine intestinal tract. Cell Rep. 27, 2665–2678.e3 (2019).
pubmed: 31141690
pmcid: 6547020
van der Post, S. et al. Site-specific O-glycosylation on the MUC2 mucin protein inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease (RgpB). J. Biol. Chem. 288, 14636–14646 (2013).
pubmed: 23546879
pmcid: 3656315
Haider, K. et al. Production of mucinase and neuraminidase and binding of Shigella to intestinal mucin. J. Diarrhoeal Dis. Res. 11, 88–92 (1993).
pubmed: 8409287
Luo, Q. et al. Enterotoxigenic Escherichia coli secretes a highly conserved mucin-degrading metalloprotease to effectively engage intestinal epithelial cells. Infect. Immun. 82, 509–521 (2014).
pubmed: 24478067
pmcid: 3911403
Gibold, L. et al. The Vat-AIEC protease promotes crossing of the intestinal mucus layer by Crohn’s disease-associated Escherichia coli. Cell. Microbiol. 18, 617–631 (2016).
pubmed: 26499863
Schauer, D. B. & Falkow, S. Attaching and effacing locus of a Citrobacter freundii biotype that causes transmissible murine colonic hyperplasia. Infect. Immun. 61, 2486–2492 (1993).
pubmed: 8500884
pmcid: 280873
Cornelis, G. R. The Yersinia deadly kiss. J. Bacteriol. 180, 5495–5504 (1998).
pubmed: 9791096
pmcid: 107605
Levine, M. M. et al. Pathogenesis of Shigella dysenteriae 1 (Shiga) dysentery. J. Infect. Dis. 127, 261–270 (1973).
pubmed: 4631877
Hansen-Wester, I., Stecher, B. & Hensel, M. Type III secretion of Salmonella enterica serovar typhimurium translocated effectors and SseFG. Infect. Immun. 70, 1403–1409 (2002).
pubmed: 11854226
pmcid: 127782
Teschler, J. K. et al. Living in the matrix: assembly and control of Vibrio cholerae biofilms. Nat. Rev. Microbiol. 13, 255–268 (2015).
pubmed: 25895940
pmcid: 4437738
Scaletsky, I. C., Silva, M. L. & Trabulsi, L. R. Distinctive patterns of adherence of enteropathogenic Escherichia coli to HeLa cells. Infect. Immun. 45, 534–536 (1984).
pubmed: 6146569
pmcid: 263286
Nikitas, G. et al. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin. J. Exp. Med. 208, 2263–2277 (2011).
pubmed: 21967767
pmcid: 3201198
Van Houdt, R. & Michiels, C. W. Role of bacterial cell surface structures in Escherichia coli biofilm formation. Res. Microbiol. 156, 626–633 (2005).
pubmed: 15950122
Sansonetti, P. J. & Phalipon, A. M cells as ports of entry for enteroinvasive pathogens: mechanisms of interaction, consequences for the disease process. Semin. Immunol. 11, 193–203 (1999).
pubmed: 10381865
Fasciano, A. C. et al. Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers. Gut Microbes 13, 1988390 (2021).
pubmed: 34793276
pmcid: 8604394
Clark, M. A., Jepson, M. A., Simmons, N. L. & Hirst, B. H. Preferential interaction of Salmonella typhimurium with mouse Peyer’s patch M cells. Res. Microbiol. 145, 543–552 (1994).
pubmed: 7855440
Wassef, J. S., Keren, D. F. & Mailloux, J. L. Role of M cells in initial antigen uptake and in ulcer formation in the rabbit intestinal loop model of shigellosis. Infect. Immun. 57, 858–863 (1989).
pubmed: 2645214
pmcid: 313189
Grützkau, A., Hanski, C., Hahn, H. & Riecken, E. O. Involvement of M cells in the bacterial invasion of Peyer’s patches: a common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria. Gut 31, 1011–1015 (1990).
pubmed: 2210445
pmcid: 1378659
Kim, M., Fevre, C., Lavina, M., Disson, O. & Lecuit, M. Live imaging reveals Listeria hijacking of E-cadherin recycling as it crosses the intestinal barrier. Curr. Biol. 31, 1037–1047.e4 (2021).
pubmed: 33333010
Linden, S. K. et al. Listeria monocytogenes internalins bind to the human intestinal mucin MUC2. Arch. Microbiol. 190, 101–104 (2008).
pubmed: 18327567
Hohmann, A. W., Schmidt, G. & Rowley, D. Intestinal colonization and virulence of Salmonella in mice. Infect. Immun. 22, 763–770 (1978).
pubmed: 365768
pmcid: 422226
Tran, E. N. H. et al. Shigella flexneri targets human colonic goblet cells by O antigen binding to sialyl-Tn and Tn antigens via glycan–glycan interactions. ACS Infect. Dis. 6, 2604–2615 (2020).
pubmed: 32926786
Clark, M. A., Hirst, B. H. & Jepson, M. A. M-cell surface β1 integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer’s patch M cells. Infect. Immun. 66, 1237–1243 (1998).
pubmed: 9488419
pmcid: 108039
Knoop, K. A. et al. Maternal activation of the EGFR prevents translocation of gut-residing pathogenic Escherichia coli in a model of late-onset neonatal sepsis. Proc. Natl Acad. Sci. USA 117, 7941–7949 (2020).
pubmed: 32179676
pmcid: 7148560
Liang, K., Wei, L. & Chen, L. Exocytosis, endocytosis, and their coupling in excitable cells. Front. Mol. Neurosci. 10, 109 (2017).
pubmed: 28469555
pmcid: 5395637
Wu, L. G., Hamid, E., Shin, W. & Chiang, H. C. Exocytosis and endocytosis: modes, functions, and coupling mechanisms. Annu. Rev. Physiol. 76, 301–331 (2014).
pubmed: 24274740
Cortez, V. et al. Astrovirus infects actively secreting goblet cells and alters the gut mucus barrier. Nat. Commun. 11, 2097 (2020).
pubmed: 32350281
pmcid: 7190700
Ingle, H. et al. Murine astrovirus tropism for goblet cells and enterocytes facilitates an IFN-λ response in vivo and in enteroid cultures. Mucosal Immunol. 14, 751–761 (2021).
pubmed: 33674763
pmcid: 8085034
Good, C., Wells, A. I. & Coyne, C. B. Type III interferon signaling restricts enterovirus 71 infection of goblet cells. Sci. Adv. 5, eaau4255 (2019).
pubmed: 30854425
pmcid: 6402847
Holly, M. K. & Smith, J. G. Adenovirus infection of human enteroids reveals interferon sensitivity and preferential infection of goblet cells. J. Virol. https://doi.org/10.1128/JVI.00250-18 (2018).
doi: 10.1128/JVI.00250-18
pubmed: 29467318
pmcid: 5899204
Cortez, V. & Schultz-Cherry, S. The role of goblet cells in viral pathogenesis. FEBS J. 288, 7060–7072 (2021).
pubmed: 33507606
pmcid: 8013445
Holm, L. & Phillipson, M. Assessment of mucus thickness and production in situ. Methods Mol. Biol. 842, 217–227 (2012).
pubmed: 22259138
Vunjak-Novakovic, G., Ronaldson-Bouchard, K. & Radisic, M. Organs-on-a-chip models for biological research. Cell 184, 4597–4611 (2021).
pubmed: 34478657
pmcid: 8417425
Sato, T. & Clevers, H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340, 1190–1194 (2013).
pubmed: 23744940
VanDussen, K. L. et al. Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays. Gut 64, 911–920 (2015).
pubmed: 25007816
Wang, Y., Kim, R., Sims, C. E. & Allbritton, N. L. Building a thick mucus hydrogel layer to improve the physiological relevance of in vitro primary colonic epithelial models. Cell. Mol. Gastroenterol. Hepatol. 8, 653–655.e5 (2019).
pubmed: 31356887
pmcid: 6889783
Knoop, K. A. et al. In vivo labeling of epithelial cell-associated antigen passages in the murine intestine. Lab. Anim. 49, 79–88 (2020).
Johansson, M. E. V. & Hansson, G. C. in Mucins: Methods and Protocols (eds McGuckin, M. A. & Thornton, D. J.) 229–235 (Humana, 2012).
Johansson, M. E. V. & Hansson, G. C. in Mucins: Methods and Protocols (eds McGuckin, M. A. & Thornton, D. J.) 109–121 (Humana, 2012).
Miyoshi, H. & Stappenbeck, T. S. In vitro expansion and genetic modification of gastrointestinal stem cells in spheroid culture. Nat. Protoc. 8, 2471–2482 (2013).
pubmed: 24232249
pmcid: 3969856
Sato, T. et al. Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009).
pubmed: 19329995
Moriya, S. et al. Macrolide antibiotics block autophagy flux and sensitize to bortezomib via endoplasmic reticulum stress-mediated CHOP induction in myeloma cells. Int. J. Oncol. 42, 1541–1550 (2013).
pubmed: 23546223
pmcid: 3661227
van der Post, S., Birchenough, G. M. H. & Held, J. M. NOX1-dependent redox signaling potentiates colonic stem cell proliferation to adapt to the intestinal microbiota by linking EGFR and TLR activation. Cell Rep. 35, 108949 (2021).
pubmed: 33826887
Liu, J., Walker, N. M., Ootani, A., Strubberg, A. M. & Clarke, L. L. Defective goblet cell exocytosis contributes to murine cystic fibrosis-associated intestinal disease. J. Clin. Invest. 125, 1056–1068 (2015).
pubmed: 25642775
pmcid: 4362271
Wang, Y. et al. Long-term culture captures injury–repair cycles of colonic stem cells. Cell 179, 1144–1159.e15 (2019).
pubmed: 31708126
pmcid: 6904908
Wang, Y. et al. A microengineered collagen scaffold for generating a polarized crypt–villus architecture of human small intestinal epithelium. Biomaterials 128, 44–55 (2017).
pubmed: 28288348
pmcid: 5392043
Wang, Y. et al. Formation of human colonic crypt array by application of chemical gradients across a shaped epithelial monolayer. Cell. Mol. Gastroenterol. Hepatol. 5, 113–130 (2018).
pubmed: 29693040
Nikolaev, M. et al. Homeostatic mini-intestines through scaffold-guided organoid morphogenesis. Nature 585, 574–578 (2020).
pubmed: 32939089
Dutton, J. S., Hinman, S. S., Kim, R., Wang, Y. & Allbritton, N. L. Primary cell-derived intestinal models: recapitulating physiology. Trends Biotechnol. 37, 744–760 (2019).
pubmed: 30591184