Efficient enzyme-free method to assess the development and maturation of the innate and adaptive immune systems in the mouse colon.
Lymphoid cells
Mechanical dissociation
Mouse colon
Multi-color flow cytometry
Myeloid cells
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 05 2024
14 05 2024
Historique:
received:
08
01
2024
accepted:
10
05
2024
medline:
15
5
2024
pubmed:
15
5
2024
entrez:
14
5
2024
Statut:
epublish
Résumé
Researchers who aim to globally analyze the gastrointestinal immune system via flow cytometry have many protocol options to choose from, with specifics generally tied to gut wall layers of interest. To get a clearer idea of the approach we should use on full-thickness colon samples from mice, we first undertook a systematic comparison of three tissue dissociation techniques: two based on enzymatic cocktails and the other one based on manual crushing. Using flow cytometry panels of general markers of lymphoid and myeloid cells, we found that the presence of cell-surface markers and relative cell population frequencies were more stable with the mechanical method. Both enzymatic approaches were associated with a marked decrease of several cell-surface markers. Using mechanical dissociation, we then developed two minimally overlapping panels, consisting of a total of 26 antibodies, for serial profiling of lymphoid and myeloid lineages from the mouse colon in greater detail. Here, we highlight how we accurately delineate these populations by manual gating, as well as the reproducibility of our panels on mouse spleen and whole blood. As a proof-of-principle of the usefulness of our general approach, we also report segment- and life stage-specific patterns of immune cell profiles in the colon. Overall, our data indicate that mechanical dissociation is more suitable and efficient than enzymatic methods for recovering immune cells from all colon layers at once. Additionally, our panels will provide researchers with a relatively simple tool for detailed immune cell profiling in the murine gastrointestinal tract, regardless of life stage or experimental conditions.
Identifiants
pubmed: 38744932
doi: 10.1038/s41598-024-61834-5
pii: 10.1038/s41598-024-61834-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11063Subventions
Organisme : CIHR
ID : PJT-180290
Pays : Canada
Informations de copyright
© 2024. The Author(s).
Références
Peterson, C. T., Sharma, V., Elmen, L. & Peterson, S. N. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota. Clin. Exp. Immunol. 179, 363–377. https://doi.org/10.1111/cei.12474 (2015).
doi: 10.1111/cei.12474
pubmed: 25345825
pmcid: 4337670
Owens, B. M. & Simmons, A. Intestinal stromal cells in mucosal immunity and homeostasis. Mucosal. Immunol. 6, 224–234. https://doi.org/10.1038/mi.2012.125 (2013).
doi: 10.1038/mi.2012.125
pubmed: 23235744
Lin, S. et al. Mucosal immunity–mediated modulation of the gut microbiome by oral delivery of probiotics into Peyer’s patches. Sci. Adv. 7, 1–15 (2021).
doi: 10.1126/sciadv.abf0677
Okumura, R. & Takeda, K. Maintenance of gut homeostasis by the mucosal immune system. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 92, 423–435. https://doi.org/10.2183/pjab.92.423 (2016).
doi: 10.2183/pjab.92.423
pubmed: 27840390
pmcid: 5328791
Smith, P. D. et al. Intestinal macrophages and response to microbial encroachment. Mucosal. Immunol. 4, 31–42. https://doi.org/10.1038/mi.2010.66 (2011).
doi: 10.1038/mi.2010.66
pubmed: 20962772
Schneider, K. M., Kim, J., Bahnsen, K., Heuckeroth, R. O. & Thaiss, C. A. Environmental perception and control of gastrointestinal immunity by the enteric nervous system. Trends Mol. Med. 28, 989–1005. https://doi.org/10.1016/j.molmed.2022.09.005 (2022).
doi: 10.1016/j.molmed.2022.09.005
pubmed: 36208986
Wu, H. J. & Wu, E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut. Microbes 3, 4–14. https://doi.org/10.4161/gmic.19320 (2012).
doi: 10.4161/gmic.19320
pubmed: 22356853
pmcid: 3337124
Hine, A. M. & Loke, P. Intestinal Macrophages in Resolving Inflammation. J. Immunol. 203, 593–599. https://doi.org/10.4049/jimmunol.1900345 (2019).
doi: 10.4049/jimmunol.1900345
pubmed: 31332080
Chung, H. & Kasper, D. L. Microbiota-stimulated immune mechanisms to maintain gut homeostasis. Curr. Opin. Immunol. 22, 455–460. https://doi.org/10.1016/j.coi.2010.06.008 (2010).
doi: 10.1016/j.coi.2010.06.008
pubmed: 20656465
Landreth, K. S. Critical windows in development of the rodent immune system. HET. 21, 493–498 (2002).
Fujiwara, H. et al. Promoting roles of embryonic signals in embryo implantation and placentation in cooperation with endocrine and immune systems. Int. J. Mol. Sci. 21, 1. https://doi.org/10.3390/ijms21051885 (2020).
doi: 10.3390/ijms21051885
Fujiwara, H. Immune cells contribute to systemic cross-talk between the embryo and mother during early pregnancy in cooperation with the endocrine system. Reprod. Med. Biol. 5, 19–29. https://doi.org/10.1111/j.1447-0578.2006.00119.x (2006).
doi: 10.1111/j.1447-0578.2006.00119.x
pubmed: 29699232
pmcid: 5906956
Kobayashi, M. & Yoshimoto, M. Multiple waves of fetal-derived immune cells constitute adult immune system. Immunol. Rev. 315, 11–30. https://doi.org/10.1111/imr.13192 (2023).
doi: 10.1111/imr.13192
pubmed: 36929134
pmcid: 10754384
Mor, G. & Cardenas, I. The immune system in pregnancy: a unique complexity. Am. J. Reprod. Immunol. 63, 425–433. https://doi.org/10.1111/j.1600-0897.2010.00836.x (2010).
doi: 10.1111/j.1600-0897.2010.00836.x
pubmed: 20367629
pmcid: 3025805
Morelli, S., Mandal, M., Goldsmith, L. T., Kashani, B. N. & Ponzio, N. M. The maternal immune system during pregnancy and its influence on fetal development. Res. Rep. Biol. https://doi.org/10.2147/rrb.S80652 (2015).
doi: 10.2147/rrb.S80652
Hoeffel, G. et al. C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 42, 665–678. https://doi.org/10.1016/j.immuni.2015.03.011 (2015).
doi: 10.1016/j.immuni.2015.03.011
pubmed: 25902481
pmcid: 4545768
Rosado, M. M. et al. From the fetal liver to spleen and gut: The highway to natural antibody. Mucosal. Immunol. 2, 351–361. https://doi.org/10.1038/mi.2009.15 (2009).
doi: 10.1038/mi.2009.15
pubmed: 19421184
Rackaityte, E. & Halkias, J. Mechanisms of fetal T cell tolerance and immune regulation. Front. Immunol. 11, 588. https://doi.org/10.3389/fimmu.2020.00588 (2020).
doi: 10.3389/fimmu.2020.00588
pubmed: 32328065
pmcid: 7160249
Dzidic, M., Boix-Amoros, A., Selma-Royo, M., Mira, A. & Collado, M. C. Gut microbiota and mucosal immunity in the neonate. Med. Sci. (Basel) 6, 1. https://doi.org/10.3390/medsci6030056 (2018).
doi: 10.3390/medsci6030056
Geuking, M. B., Koller, Y., Rupp, S. & McCoy, K. D. The interplay between the gut microbiota and the immune system. Gut. Microbes 5, 411–418. https://doi.org/10.4161/gmic.29330 (2014).
doi: 10.4161/gmic.29330
pubmed: 24922519
pmcid: 4153781
Stras, S. F. et al. Maturation of the human intestinal immune system occurs early in fetal development. Dev. Cell 51, 357–373. https://doi.org/10.1016/j.devcel.2019.09.008 (2019).
doi: 10.1016/j.devcel.2019.09.008
pubmed: 31607651
Sanidad, K. Z. & Zeng, M. Y. Neonatal gut microbiome and immunity. Curr. Opin. Microbiol. 56, 30–37. https://doi.org/10.1016/j.mib.2020.05.011 (2020).
doi: 10.1016/j.mib.2020.05.011
pubmed: 32634598
pmcid: 8729197
Tsafaras, G. P., Ntontsi, P. & Xanthou, G. Advantages and limitations of the neonatal immune system. Front. Pediatr. 8, 5. https://doi.org/10.3389/fped.2020.00005 (2020).
doi: 10.3389/fped.2020.00005
pubmed: 32047730
pmcid: 6997472
Battersby, A. J. & Gibbons, D. L. The gut mucosal immune system in the neonatal period. Pediatr. Allergy Immunol. 24, 414–421. https://doi.org/10.1111/pai.12079 (2013).
doi: 10.1111/pai.12079
pubmed: 23682966
Schill, E. M., Floyd, A. N. & Newberry, R. D. Neonatal development of intestinal neuroimmune interactions. Trends Neurosci. 45, 928–941. https://doi.org/10.1016/j.tins.2022.10.002 (2022).
doi: 10.1016/j.tins.2022.10.002
pubmed: 36404456
pmcid: 9683521
Parada Venegas, D. et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol. 10, 277. https://doi.org/10.3389/fimmu.2019.00277 (2019).
doi: 10.3389/fimmu.2019.00277
pubmed: 30915065
pmcid: 6421268
Yao, Y. et al. The role of short-chain fatty acids in immunity, inflammation and metabolism. Crit. Rev. Food Sci. Nutr. 62, 1–12. https://doi.org/10.1080/10408398.2020.1854675 (2022).
doi: 10.1080/10408398.2020.1854675
pubmed: 33261516
Correa-Oliveira, R., Fachi, J. L., Vieira, A., Sato, F. T. & Vinolo, M. A. Regulation of immune cell function by short-chain fatty acids. Clin. Transl. Immunol. 5, e73. https://doi.org/10.1038/cti.2016.17 (2016).
doi: 10.1038/cti.2016.17
Ratajczak, W. et al. Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs). Acta Biochim Polut. 66, 1–12. https://doi.org/10.18388/abp.2018_2648 (2019).
doi: 10.18388/abp.2018_2648
Soret, R. et al. Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. Gastroenterology 138, 1772–1782. https://doi.org/10.1053/j.gastro.2010.01.053 (2010).
doi: 10.1053/j.gastro.2010.01.053
pubmed: 20152836
Suply, E., de Vries, P., Soret, R., Cossais, F. & Neunlist, M. Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G1373–G1380. https://doi.org/10.1152/ajpgi.00338.2011 (2012).
doi: 10.1152/ajpgi.00338.2011
pubmed: 22492692
Simon, A. K., Hollander, G. A. & McMichael, A. Evolution of the immune system in humans from infancy to old age. Proc. Biol. Sci. 282, 20143085. https://doi.org/10.1098/rspb.2014.3085 (2015).
doi: 10.1098/rspb.2014.3085
pubmed: 26702035
pmcid: 4707740
Bain, C. C. et al. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat. Immunol. 15, 929–937. https://doi.org/10.1038/ni.2967 (2014).
doi: 10.1038/ni.2967
pubmed: 25151491
pmcid: 4169290
Wiertsema, S. P., van Bergenhenegouwen, J., Garssen, J. & Knippels, L. M. J. The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies. Nutrients 13, 1. https://doi.org/10.3390/nu13030886 (2021).
doi: 10.3390/nu13030886
Chassaing, B., Kumar, M., Baker, M. T., Singh, V. & Vijay-Kumar, M. Mammalian gut immunity. Biomed. J. 37, 246–258. https://doi.org/10.4103/2319-4170.130922 (2014).
doi: 10.4103/2319-4170.130922
pubmed: 25163502
Arya, A. K. & Hu, B. Brain-gut axis after stroke. Brain Circ. 4, 165–173. https://doi.org/10.4103/bc.bc_32_18 (2018).
doi: 10.4103/bc.bc_32_18
pubmed: 30693343
pmcid: 6329216
Guo, Y. et al. The gut-organ-axis concept: Advances the application of gut-on-chip technology. Int. J. Mol. Sci. 24, 1. https://doi.org/10.3390/ijms24044089 (2023).
doi: 10.3390/ijms24044089
Schreurs, R. et al. Quantitative comparison of human intestinal mononuclear leukocyte isolation techniques for flow cytometric analyses. J. Immunol. Methods 445, 45–52. https://doi.org/10.1016/j.jim.2017.03.006 (2017).
doi: 10.1016/j.jim.2017.03.006
pubmed: 28274838
Jorgensen, P. B. et al. Identification, isolation and analysis of human gut-associated lymphoid tissues. Nat. Protoc. 16, 2051–2067. https://doi.org/10.1038/s41596-020-00482-1 (2021).
doi: 10.1038/s41596-020-00482-1
pubmed: 33619391
Stzepourginski, I., Eberl, G. & Peduto, L. An optimized protocol for isolating lymphoid stromal cells from the intestinal lamina propria. J. Immunol. Methods 421, 14–19. https://doi.org/10.1016/j.jim.2014.11.013 (2015).
doi: 10.1016/j.jim.2014.11.013
pubmed: 25599879
Smith, P. D. et al. Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J. Immunol. 167, 2651–2656. https://doi.org/10.4049/jimmunol.167.5.2651 (2001).
doi: 10.4049/jimmunol.167.5.2651
pubmed: 11509607
Pabst, O. & Bernhardt, G. The puzzle of intestinal lamina propria dendritic cells and macrophages. Eur. J. Immunol. 40, 2107–2111. https://doi.org/10.1002/eji.201040557 (2010).
doi: 10.1002/eji.201040557
pubmed: 20853495
Ozaki, H. et al. Isolation and characterization of resident macrophages from the smooth muscle layers of murine small intestine. Neurogastroenterol. Motil. 16, 39–51. https://doi.org/10.1046/j.1365-2982.2003.00461.x (2004).
doi: 10.1046/j.1365-2982.2003.00461.x
pubmed: 14764204
Avetisyan, M. et al. Muscularis macrophage development in the absence of an enteric nervous system. Proc. Natl. Acad. Sci. USA 115, 4696–4701. https://doi.org/10.1073/pnas.1802490115 (2018).
doi: 10.1073/pnas.1802490115
pubmed: 29666241
pmcid: 5939112
Muller, P. A. et al. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158, 300–313. https://doi.org/10.1016/j.cell.2014.04.050 (2014).
doi: 10.1016/j.cell.2014.04.050
pubmed: 25036630
pmcid: 4149228
Zhou, L. et al. New insights into muscularis macrophages in the gut: from their origin to therapeutic targeting. Immunol. Res. https://doi.org/10.1007/s12026-023-09397-x (2023).
doi: 10.1007/s12026-023-09397-x
pubmed: 38135837
pmcid: 10247270
Becker, L., Spear, E. T., Sinha, S. R., Haileselassie, Y. & Habtezion, A. Age-related changes in gut microbiota alter phenotype of muscularis macrophages and disrupt gastrointestinal motility. Cell. Mol. Gastroenterol. Hepatol. 7, 243–245. https://doi.org/10.1016/j.jcmgh.2018.09.001 (2019).
doi: 10.1016/j.jcmgh.2018.09.001
pubmed: 30585161
Singh, A., Blanco, A., Sinnott, R. & Knaus, U. Rapid isolation and flow cytometry analysis of murine intestinal immune cells after chemically induced colitis. Bio-protocol 11, 11. https://doi.org/10.21769/BioProtoc.4182 (2021).
doi: 10.21769/BioProtoc.4182
Tamura, A. et al. Distribution of two types of lymphocytes (intraepithelial and lamina-propria-associated) in the murine small intestine. Cell Tiss. Res. 313, 47–53. https://doi.org/10.1007/s00441-003-0706-4 (2003).
doi: 10.1007/s00441-003-0706-4
Yero, A. et al. Impact of early ARV initiation on relative proportions of effector and regulatory CD8 T cell in mesenteric lymph nodes and peripheral blood during acute SIV infection of rhesus macaques. J. Virol. 96, e0025522. https://doi.org/10.1128/jvi.00255-22 (2022).
doi: 10.1128/jvi.00255-22
pubmed: 35311550
Bondonese, A. et al. Impact of enzymatic digestion on single cell suspension yield from peripheral human lung tissue. Cytometry A 103, 777–785. https://doi.org/10.1002/cyto.a.24777 (2023).
doi: 10.1002/cyto.a.24777
pubmed: 37449375
Goodyear, A. W., Kumar, A., Dow, S. & Ryan, E. P. Optimization of murine small intestine leukocyte isolation for global immune phenotype analysis. J. Immunol. Methods 405, 97–108. https://doi.org/10.1016/j.jim.2014.01.014 (2014).
doi: 10.1016/j.jim.2014.01.014
pubmed: 24508527
Pham, T. N. Q. et al. Flt3L-mediated expansion of plasmacytoid dendritic cells suppresses HIV infection in humanized mice. Cell reports 29, 2770–2782. https://doi.org/10.1016/j.celrep.2019.10.094 (2019).
doi: 10.1016/j.celrep.2019.10.094
pubmed: 31775044
Nemoto, S., Mailloux, A. W., Kroeger, J. & Mule, J. J. OMIP-031: Immunologic checkpoint expression on murine effector and memory T-cell subsets. Cytomet. A 89, 427–429. https://doi.org/10.1002/cyto.a.22808 (2016).
doi: 10.1002/cyto.a.22808
DiPiazza, A. T., Hill, J. P., Graham, B. S. & Ruckwardt, T. J. OMIP-061: 20-Color flow cytometry panel for high-dimensional characterization of murine antigen-presenting cells. Cytomet. A 95, 1226–1230. https://doi.org/10.1002/cyto.a.23880 (2019).
doi: 10.1002/cyto.a.23880
Mincham, K. T., Young, J. D. & Strickland, D. H. OMIP 076: High-dimensional immunophenotyping of murine T-cell, B-cell, and antibody secreting cell subsets. Cytomet. A 99, 888–892. https://doi.org/10.1002/cyto.a.24474 (2021).
doi: 10.1002/cyto.a.24474
Percie du Sert, N. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol 18, e3000410. https://doi.org/10.1371/journal.pbio.3000410 (2020).
Soret, R. et al. Genetic background influences severity of colonic aganglionosis and response to GDNF enemas in the holstein mouse model of hirschsprung disease. Int. J. Mol. Sci. 22, 1. https://doi.org/10.3390/ijms222313140 (2021).
doi: 10.3390/ijms222313140
Soret, R. et al. A collagen VI-dependent pathogenic mechanism for Hirschsprung’s disease. J. Clin. Invest. 125, 4483–4496. https://doi.org/10.1172/JCI83178 (2015).
doi: 10.1172/JCI83178
pubmed: 26571399
pmcid: 4665793
Soret, R. et al. Glial cell derived neurotrophic factor induces enteric neurogenesis and improves colon structure and function in mouse models of Hirschsprung disease. Gastroenterology 159, 1824-1838.e1817. https://doi.org/10.1053/j.gastro.2020.07.018 (2020).
doi: 10.1053/j.gastro.2020.07.018
pubmed: 32687927
Brandi, J., Wiethe, C., Riehn, M. & Jacobs, T. OMIP-93: A 41-color high parameter panel to characterize various co-inhibitory molecules and their ligands in the lymphoid and myeloid compartment in mice. Cytomet. A 103, 624–630. https://doi.org/10.1002/cyto.a.24740 (2023).
doi: 10.1002/cyto.a.24740
Cossarizza, A. et al. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur. J. Immunol. 49, 1457–1973. https://doi.org/10.1002/eji.201970107 (2019).
doi: 10.1002/eji.201970107
pubmed: 31633216
pmcid: 7350392
Jarade, A., Di Santo, J. P. & Serafini, N. Group 3 innate lymphoid cells mediate host defense against attaching and effacing pathogens. Curr. Opin. Microbiol. 63, 83–91. https://doi.org/10.1016/j.mib.2021.06.005 (2021).
doi: 10.1016/j.mib.2021.06.005
pubmed: 34274597
Joeris, T., Muller-Luda, K., Agace, W. W. & Mowat, A. M. Diversity and functions of intestinal mononuclear phagocytes. Mucosal. Immunol. 10, 845–864. https://doi.org/10.1038/mi.2017.22 (2017).
doi: 10.1038/mi.2017.22
pubmed: 28378807
Withers, D. R. & Hepworth, M. R. Group 3 innate lymphoid cells: Communications hubs of the intestinal immune system. Front. Immunol. 8, 1298. https://doi.org/10.3389/fimmu.2017.01298 (2017).
doi: 10.3389/fimmu.2017.01298
pubmed: 29085366
pmcid: 5649144
Yero, A. et al. Dynamics and epigenetic signature of regulatory T-cells following antiretroviral therapy initiation in acute HIV infection. EBioMedicine 71, 103570. https://doi.org/10.1016/j.ebiom.2021.103570 (2021).
doi: 10.1016/j.ebiom.2021.103570
pubmed: 34500304
pmcid: 8429924
Autengruber, A., Gereke, M., Hansen, G., Hennig, C. & Bruder, D. Impact of enzymatic tissue disintegration on the level of surface molecule expression and immune cell function. Eur. J. Microbiol. Immunol. (Bp) 2, 112–120. https://doi.org/10.1556/EuJMI.2.2012.2.3 (2012).
doi: 10.1556/EuJMI.2.2012.2.3
pubmed: 24672679
Chen, Z. et al. Collagenase digestion down-regulates the density of CD27 on lymphocytes. J. Immunol. Methods 413, 57–61. https://doi.org/10.1016/j.jim.2014.06.017 (2014).
doi: 10.1016/j.jim.2014.06.017
pubmed: 25066632
Skulska, K., Wegrzyn, A. S., Chelmonska-Soyta, A. & Chodaczek, G. Impact of tissue enzymatic digestion on analysis of immune cells in mouse reproductive mucosa with a focus on gammadelta T cells. J. Immunol. Methods 474, 112665. https://doi.org/10.1016/j.jim.2019.112665 (2019).
doi: 10.1016/j.jim.2019.112665
pubmed: 31525366
Bondonese, A. et al. Impact of enzymatic digestion on single cell suspension yield from peripheral human lung tissue. Cytomet. A https://doi.org/10.1002/cyto.a.24777 (2023).
doi: 10.1002/cyto.a.24777
Blom, K. G. et al. Isolation of murine intrahepatic immune cells employing a modified procedure for mechanical disruption and functional characterization of the B, T and natural killer T cells obtained. Clin. Experiment. Immunol. 155, 320–329. https://doi.org/10.1111/j.1365-2249.2008.03815.x (2009).
doi: 10.1111/j.1365-2249.2008.03815.x
Bosco, N. & Noti, M. The aging gut microbiome and its impact on host immunity. Genes Immun. 22, 289–303. https://doi.org/10.1038/s41435-021-00126-8 (2021).
doi: 10.1038/s41435-021-00126-8
pubmed: 33875817
pmcid: 8054695
Walrath, T. et al. Age-related changes in intestinal immunity and the microbiome. J. Leukoc Biol. 109, 1045–1061. https://doi.org/10.1002/JLB.3RI0620-405RR (2021).
doi: 10.1002/JLB.3RI0620-405RR
pubmed: 33020981
Al Nabhani, Z. et al. A weaning reaction to microbiota is required for resistance to immunopathologies in the adult. Immunity 50, 1276–1288. https://doi.org/10.1016/j.immuni.2019.02.014 (2019).
doi: 10.1016/j.immuni.2019.02.014
pubmed: 30902637
Lubin, J. B. et al. Arresting microbiome development limits immune system maturation and resistance to infection in mice. Cell Host Microbe 31, 554–570. https://doi.org/10.1016/j.chom.2023.03.006 (2023).
doi: 10.1016/j.chom.2023.03.006
pubmed: 36996818
pmcid: 10935632
Menezes, J. S. et al. Stimulation by food proteins plays a critical role in the maturation of the immune system. Int. Immunol. 15, 447–455. https://doi.org/10.1093/intimm/dxg043 (2003).
doi: 10.1093/intimm/dxg043
pubmed: 12618489
Agace, W. W. & McCoy, K. D. Regionalized development and maintenance of the intestinal adaptive immune landscape. Immunity 46, 532–548. https://doi.org/10.1016/j.immuni.2017.04.004 (2017).
doi: 10.1016/j.immuni.2017.04.004
pubmed: 28423335
Bowcutt, R. et al. Heterogeneity across the murine small and large intestine. World J. Gastroenterol. 20, 15216–15232. https://doi.org/10.3748/wjg.v20.i41.15216 (2014).
doi: 10.3748/wjg.v20.i41.15216
pubmed: 25386070
pmcid: 4223255
Bondurand, N. & Southard-Smith, E. M. Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: Old and new players. Dev. Biol. 417, 139–157. https://doi.org/10.1016/j.ydbio.2016.06.042 (2016).
doi: 10.1016/j.ydbio.2016.06.042
pubmed: 27370713
pmcid: 5026931
Pilon, N. Pigmentation-based insertional mutagenesis is a simple and potent screening approach for identifying neurocristopathy-associated genes in mice. Rare Dis. 4, e1156287 (2016).
doi: 10.1080/21675511.2016.1156287
pubmed: 27141416
pmcid: 4838316
Pilon, N. Treatment and prevention of neurocristopathies. Trends Mol. Med. 27, 451–468. https://doi.org/10.1016/j.molmed.2021.01.009 (2021).
doi: 10.1016/j.molmed.2021.01.009
pubmed: 33627291
Heuckeroth, R. O. Hirschsprung disease—Integrating basic science and clinical medicine to improve outcomes. Nat. Rev. Gastroenterol. Hepatol. 15, 152–167. https://doi.org/10.1038/nrgastro.2017.149 (2018).
doi: 10.1038/nrgastro.2017.149
pubmed: 29300049
Montalva, L. et al. Hirschsprung disease. Nat. Rev. Dis. Primers 9, 54. https://doi.org/10.1038/s41572-023-00465-y (2023).
doi: 10.1038/s41572-023-00465-y
pubmed: 37828049
Li, S. et al. Update on the pathogenesis of the hirschsprung-associated enterocolitis. Int J Mol Sci 24, 1. https://doi.org/10.3390/ijms24054602 (2023).
doi: 10.3390/ijms24054602
Cheng, Z. et al. Murine model of Hirschsprung-associated enterocolitis. I: phenotypic characterization with development of a histopathologic grading system. J. Pediatr. Surg. 45, 475–482. https://doi.org/10.1016/j.jpedsurg.2009.06.009 (2010).
doi: 10.1016/j.jpedsurg.2009.06.009
pubmed: 20223308
pmcid: 4370315
Porokuokka, L. L. et al. Gfra1 underexpression causes Hirschsprung’s disease and Associated enterocolitis in mice. Cell. Mol. Gastroenterol. Hepatol. 7, 655–678. https://doi.org/10.1016/j.jcmgh.2018.12.007 (2019).
doi: 10.1016/j.jcmgh.2018.12.007
pubmed: 30594740
Gosain, A. et al. Impaired cellular immunity in the murine neural crest conditional deletion of endothelin receptor-B model of Hirschsprung’s disease. PLoS One 10, e0128822. https://doi.org/10.1371/journal.pone.0128822 (2015).
doi: 10.1371/journal.pone.0128822
pubmed: 26061883
pmcid: 4465674
Medrano, G. et al. B-lymphocyte-intrinsic and -extrinsic defects in secretory immunoglobulin A production in the neural crest-conditional deletion of endothelin receptor B model of Hirschsprung-associated enterocolitis. FASEB J 33, 7615–7624. https://doi.org/10.1096/fj.201801913R (2019).
doi: 10.1096/fj.201801913R
pubmed: 30908942
pmcid: 6529339
Patel, A. et al. Differential RET signaling pathways drive development of the enteric lymphoid and nervous systems. Sci. Signal. 5, 55. https://doi.org/10.1126/scisignal.2002734 (2012).
doi: 10.1126/scisignal.2002734
Veiga-Fernandes, H. et al. Tyrosine kinase receptor RET is a key regulator of Peyer’s patch organogenesis. Nature 446, 547–551. https://doi.org/10.1038/nature05597 (2007).
doi: 10.1038/nature05597
pubmed: 17322904
Frykman, P. K., Cheng, Z., Wang, X. & Dhall, D. Enterocolitis causes profound lymphoid depletion in endothelin receptor B- and endothelin 3-null mouse models of Hirschsprung-associated enterocolitis. Eur. J. Immunol. 45, 807–817. https://doi.org/10.1002/eji.201444737 (2015).
doi: 10.1002/eji.201444737
pubmed: 25487064
pmcid: 4370321
Chen, X. et al. Intestinal proinflammatory macrophages induce a phenotypic switch in interstitial cells of Cajal. J. Clin. Invest. 130, 6443–6456. https://doi.org/10.1172/JCI126584 (2020).
doi: 10.1172/JCI126584
pubmed: 32809970
pmcid: 7685750
Karim, A., Tang, C. S. & Tam, P. K. The emerging genetic landscape of hirschsprung disease and its potential clinical applications. Front. Pediatr. 9, 638093. https://doi.org/10.3389/fped.2021.638093 (2021).
doi: 10.3389/fped.2021.638093
pubmed: 34422713
pmcid: 8374333
Ibiza, S. et al. Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature 535, 440–443. https://doi.org/10.1038/nature18644 (2016).
doi: 10.1038/nature18644
pubmed: 27409807
pmcid: 4962913
Vargas-Leal, V. et al. Expression and function of glial cell line-derived neurotrophic factor family ligands and their receptors on human immune cells. J. Immunol. 175, 2301–2308. https://doi.org/10.4049/jimmunol.175.4.2301 (2005).
doi: 10.4049/jimmunol.175.4.2301
pubmed: 16081799
Mizoguchi, A. & Bhan, A. K. A case for regulatory B cells. J. Immunol. 176, 705–710. https://doi.org/10.4049/jimmunol.176.2.705 (2006).
doi: 10.4049/jimmunol.176.2.705
pubmed: 16393950
Vazquez, M. I., Catalan-Dibene, J. & Zlotnik, A. B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine 74, 318–326. https://doi.org/10.1016/j.cyto.2015.02.007 (2015).
doi: 10.1016/j.cyto.2015.02.007
pubmed: 25742773
pmcid: 4475485
Li, T., Liu, M., Sun, S., Liu, X. & Liu, D. Epithelial cells orchestrate the functions of dendritic cells in intestinal homeostasis. J. Biomed. Res. Environ. Sci. 1, 343–352. https://doi.org/10.37871/jbres1165 (2020).
doi: 10.37871/jbres1165
Shresta, S., Kyle, J. L., Robert Beatty, P. & Harris, E. Early activation of natural killer and B cells in response to primary dengue virus infection in A/J mice. Virology 319, 262–273. https://doi.org/10.1016/j.virol.2003.09.048 (2004).
doi: 10.1016/j.virol.2003.09.048
pubmed: 14980486
Kitoh, A. et al. Indispensable role of the Runx1-Cbfbeta transcription complex for in vivo-suppressive function of FoxP3+ regulatory T cells. Immunity 31, 609–620. https://doi.org/10.1016/j.immuni.2009.09.003 (2009).
doi: 10.1016/j.immuni.2009.09.003
pubmed: 19800266
Ascon, D. B. et al. Normal mouse kidneys contain activated and CD3+CD4- CD8- double-negative T lymphocytes with a distinct TCR repertoire. J Leukoc Biol 84, 1400–1409. https://doi.org/10.1189/jlb.0907651 (2008).
doi: 10.1189/jlb.0907651
pubmed: 18765477
pmcid: 2614602
Freeman, B. E., Hammarlund, E., Raue, H. P. & Slifka, M. K. Regulation of innate CD8+ T-cell activation mediated by cytokines. Proc. Natl. Acad. Sci. USA 109, 9971–9976. https://doi.org/10.1073/pnas.1203543109 (2012).
doi: 10.1073/pnas.1203543109
pubmed: 22665806
pmcid: 3382521
Keir, M., Yi, Y., Lu, T. & Ghilardi, N. The role of IL-22 in intestinal health and disease. J. Exp. Med. 217, e20192195. https://doi.org/10.1084/jem.20192195 (2020).
doi: 10.1084/jem.20192195
pubmed: 32997932
pmcid: 7062536
Li, H. & Tsokos, G. C. Double-negative T cells in autoimmune diseases. Curr. Opin. Rheumatol. 33, 163–172. https://doi.org/10.1097/BOR.0000000000000778 (2021).
doi: 10.1097/BOR.0000000000000778
pubmed: 33394752
pmcid: 8018563
Wu, Z. et al. CD3(+)CD4(−)CD8(−) (Double-Negative) T cells in inflammation, immune disorders and cancer. Front. Immunol. 13, 816005. https://doi.org/10.3389/fimmu.2022.816005 (2022).
doi: 10.3389/fimmu.2022.816005
pubmed: 35222392
pmcid: 8866817
Rodriguez-Galán, M. C., Bream, J. H., Farr, A. & Young, H. A. Synergistic effect of IL-2, IL-12, and IL-18 on thymocyte apoptosis and Th1/Th2 cytokine expression. J. Immunol. 174, 2796–2804. https://doi.org/10.4049/jimmunol.174.5.2796 (2005).
doi: 10.4049/jimmunol.174.5.2796
pubmed: 15728489
Parra, M. et al. Memory CD73+IgM+ B cells protect against Plasmodium yoelii infection and express Granzyme B. PLoS One 15, e0238493. https://doi.org/10.1371/journal.pone.0238493 (2020).
doi: 10.1371/journal.pone.0238493
pubmed: 32886698
pmcid: 7473529
Nascimento, D. C. et al. Sepsis expands a CD39(+) plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity. Immunity 54, 2024–2041. https://doi.org/10.1016/j.immuni.2021.08.005 (2021).
doi: 10.1016/j.immuni.2021.08.005
pubmed: 34473957
Sallusto, F. & Lanzavecchia, A. Heterogeneity of CD4+ memory T cells: Functional modules for tailored immunity. Eur. J. Immunol. 39, 2076–2082. https://doi.org/10.1002/eji.200939722 (2009).
doi: 10.1002/eji.200939722
pubmed: 19672903
Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498. https://doi.org/10.1016/j.cell.2009.09.033 (2009).
doi: 10.1016/j.cell.2009.09.033
pubmed: 19836068
pmcid: 2796826
Feng, T. et al. Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J. Immunol. 186, 6313–6318. https://doi.org/10.4049/jimmunol.1001454 (2011).
doi: 10.4049/jimmunol.1001454
pubmed: 21531892
Rogers, P. R., Huston, G. & Swain, S. L. High antigen density and IL-2 are required for generation of CD4 effectors secreting Th1 rather than Th0 cytokines. J. Immunol. 161, 3844–3852. https://doi.org/10.4049/jimmunol.161.8.3844 (1998).
doi: 10.4049/jimmunol.161.8.3844
pubmed: 9780149
Srivastava, R. K., Dar, H. Y. & Mishra, P. K. Immunoporosis: Immunology of osteoporosis-role of T cells. Front. Immunol. 9, 657. https://doi.org/10.3389/fimmu.2018.00657 (2018).
doi: 10.3389/fimmu.2018.00657
pubmed: 29675022
pmcid: 5895643
Shevchenko, I. et al. Enhanced expression of CD39 and CD73 on T cells in the regulation of anti-tumor immune responses. Oncoimmunology 9, 1744946. https://doi.org/10.1080/2162402X.2020.1744946 (2020).
doi: 10.1080/2162402X.2020.1744946
pubmed: 33457090
pmcid: 7790505
Ono-Ohmachi, A. et al. Effector memory CD4(+)T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance. Mucosal Immunol. 14, 1335–1346. https://doi.org/10.1038/s41385-021-00434-2 (2021).
doi: 10.1038/s41385-021-00434-2
pubmed: 34326478
Cho, M. J. et al. Steady-state memory-phenotype conventional CD4(+) T cells exacerbate autoimmune neuroinflammation in a bystander manner via the Bhlhe40/GM-CSF axis. Exp. Mol. Med. 55, 1033–1045. https://doi.org/10.1038/s12276-023-00995-1 (2023).
doi: 10.1038/s12276-023-00995-1
pubmed: 37121980
pmcid: 10238403
Lee, H. G. et al. Pathogenic function of bystander-activated memory-like CD4(+) T cells in autoimmune encephalomyelitis. Nat. Commun. 10, 709. https://doi.org/10.1038/s41467-019-08482-w (2019).
doi: 10.1038/s41467-019-08482-w
pubmed: 30755603
pmcid: 6372661
Dobson, H. E. et al. Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance. Mucosal Immunol. 13, 518–529. https://doi.org/10.1038/s41385-019-0244-3 (2020).
doi: 10.1038/s41385-019-0244-3
pubmed: 31900406
pmcid: 7183437
Wilk, M. M. et al. Lung CD4 tissue-resident memory T cells mediate adaptive immunity induced by previous infection of mice with Bordetella pertussis. J. Immunol. 199, 233–243. https://doi.org/10.4049/jimmunol.1602051 (2017).
doi: 10.4049/jimmunol.1602051
pubmed: 28533445
Chen, B. et al. TIGIT deficiency protects mice from DSS-induced colitis by regulating IL-17A-producing CD4(+) tissue-resident memory T cells. Front. Immunol. 13, 931761. https://doi.org/10.3389/fimmu.2022.931761 (2022).
doi: 10.3389/fimmu.2022.931761
pubmed: 35844584
pmcid: 9283574
Maddaloni, M. et al. Milk-based nutraceutical for treating autoimmune arthritis via the stimulation of IL-10- and TGF-beta-producing CD39+ regulatory T cells. PLoS One 10, e0117825. https://doi.org/10.1371/journal.pone.0117825 (2015).
doi: 10.1371/journal.pone.0117825
pubmed: 25629976
pmcid: 4309564
Kochetkova, I., Thornburg, T., Callis, G. & Pascual, D. W. Segregated regulatory CD39+CD4+ T cell function: TGF-beta-producing Foxp3- and IL-10-producing Foxp3+ cells are interdependent for protection against collagen-induced arthritis. J. Immunol. 187, 4654–4666. https://doi.org/10.4049/jimmunol.1100530 (2011).
doi: 10.4049/jimmunol.1100530
pubmed: 21967895
Fina, D. et al. Regulation of gut inflammation and th17 cell response by interleukin-21. Gastroenterology 134, 1038–1048. https://doi.org/10.1053/j.gastro.2008.01.041 (2008).
doi: 10.1053/j.gastro.2008.01.041
pubmed: 18395085
Yu, L. et al. CD69 enhances immunosuppressive function of regulatory T-cells and attenuates colitis by prompting IL-10 production. Cell Death Dis. 9, 905. https://doi.org/10.1038/s41419-018-0927-9 (2018).
doi: 10.1038/s41419-018-0927-9
pubmed: 30185773
pmcid: 6125584
Noble, A., Giorgini, A. & Leggat, J. A. Cytokine-induced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage. Blood 107, 4475–4483. https://doi.org/10.1182/blood-2005-10-3994 (2006).
doi: 10.1182/blood-2005-10-3994
pubmed: 16467201
Alam, M. S., Cavanaugh, C., Pereira, M., Babu, U. & Williams, K. Susceptibility of aging mice to listeriosis: Role of anti-inflammatory responses with enhanced Treg-cell expression of CD39/CD73 and Th-17 cells. Int. J. Med. Microbiol. 310, 151397. https://doi.org/10.1016/j.ijmm.2020.151397 (2020).
doi: 10.1016/j.ijmm.2020.151397
pubmed: 31974050
Ochoa-Reparaz, J. et al. Induction of gut regulatory CD39(+) T cells by teriflunomide protects against EAE. Neurol. Neuroimmunol. Neuroinflam. 3, e291. https://doi.org/10.1212/NXI.0000000000000291 (2016).
doi: 10.1212/NXI.0000000000000291
Zhou, L. et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 453, 236–240. https://doi.org/10.1038/nature06878 (2008).
doi: 10.1038/nature06878
pubmed: 18368049
pmcid: 2597437
Sanchez, A. M., Zhu, J., Huang, X. & Yang, Y. The development and function of memory regulatory T cells after acute viral infections. J. Immunol. 189, 2805–2814. https://doi.org/10.4049/jimmunol.1200645 (2012).
doi: 10.4049/jimmunol.1200645
pubmed: 22855712
Kleinewietfeld, M. et al. CCR6 expression defines regulatory effector/memory-like cells within the CD25(+)CD4+ T-cell subset. Blood 105, 2877–2886. https://doi.org/10.1182/blood-2004-07-2505 (2005).
doi: 10.1182/blood-2004-07-2505
pubmed: 15613550
Anthony, S. M. et al. Protective function and durability of mouse lymph node-resident memory CD8(+) T cells. Elife 10, 1. https://doi.org/10.7554/eLife.68662 (2021).
doi: 10.7554/eLife.68662
Schneider, E. et al. CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression. Nat. Commun. 12, 5911. https://doi.org/10.1038/s41467-021-26134-w (2021).
doi: 10.1038/s41467-021-26134-w
pubmed: 34625545
pmcid: 8501027
Jiang, X. et al. The ectonucleotidases CD39 and CD73 on T cells: The new pillar of hematological malignancy. Front. Immunol. 14, 1110325. https://doi.org/10.3389/fimmu.2023.1110325 (2023).
doi: 10.3389/fimmu.2023.1110325
pubmed: 36776866
pmcid: 9911447
Nath, P. R. et al. Loss of CD47 alters CD8+ T cell activation in vitro and immunodynamics in mice. Oncoimmunology 11, 2111909. https://doi.org/10.1080/2162402X.2022.2111909 (2022).
doi: 10.1080/2162402X.2022.2111909
pubmed: 36105746
pmcid: 9467551
Lykhopiy, V., Malviya, V., Humblet-Baron, S. & Schlenner, S. M. IL-2 immunotherapy for targeting regulatory T cells in autoimmunity. Genes Immun. 24, 248–262. https://doi.org/10.1038/s41435-023-00221-y (2023).
doi: 10.1038/s41435-023-00221-y
pubmed: 37741949
pmcid: 10575774
Peterson, R. A. Regulatory T-cells: Diverse phenotypes integral to immune homeostasis and suppression. Toxicol. Pathol. 40, 186–204. https://doi.org/10.1177/0192623311430693 (2012).
doi: 10.1177/0192623311430693
pubmed: 22222887
Juvet, S. C. & Zhang, L. Double negative regulatory T cells in transplantation and autoimmunity: Recent progress and future directions. J. Mol. Cell Biol. 4, 48–58. https://doi.org/10.1093/jmcb/mjr043 (2012).
doi: 10.1093/jmcb/mjr043
pubmed: 22294241
pmcid: 3269300
Aychek, T. et al. IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology. Nat. Commun. 6, 6525. https://doi.org/10.1038/ncomms7525 (2015).
doi: 10.1038/ncomms7525
pubmed: 25761673
Holland, A. M., Bon-Frauches, A. C., Keszthelyi, D., Melotte, V. & Boesmans, W. The enteric nervous system in gastrointestinal disease etiology. Cell Mol. Life Sci. 78, 4713–4733. https://doi.org/10.1007/s00018-021-03812-y (2021).
doi: 10.1007/s00018-021-03812-y
pubmed: 33770200
pmcid: 8195951
Wu, R. Q., Zhang, D. F., Tu, E., Chen, Q. M. & Chen, W. The mucosal immune system in the oral cavity-an orchestra of T cell diversity. Int. J. Oral. Sci. 6, 125–132. https://doi.org/10.1038/ijos.2014.48 (2014).
doi: 10.1038/ijos.2014.48
pubmed: 25105816
pmcid: 4170154
Bain, C. C. & Mowat, A. M. Macrophages in intestinal homeostasis and inflammation. Immunol. Rev. 260, 102–117 (2014).
doi: 10.1111/imr.12192
pubmed: 24942685
pmcid: 4141699
Viola, M. F. & Boeckxstaens, G. Intestinal resident macrophages: Multitaskers of the gut. Neurogastroenterol. Motil. 32, e13843. https://doi.org/10.1111/nmo.13843 (2020).
doi: 10.1111/nmo.13843
pubmed: 32222060
pmcid: 7757264
De Calisto, J., Villablanca, E. J. & Mora, J. R. FcgammaRI (CD64): an identity card for intestinal macrophages. Eur. J. Immunol. 42, 3136–3140. https://doi.org/10.1002/eji.201243061 (2012).
doi: 10.1002/eji.201243061
pubmed: 23255010
pmcid: 3644030
Cerovic, V., Bain, C. C., Mowat, A. M. & Milling, S. W. Intestinal macrophages and dendritic cells: what’s the difference?. Trends Immunol. 35, 270–277. https://doi.org/10.1016/j.it.2014.04.003 (2014).
doi: 10.1016/j.it.2014.04.003
pubmed: 24794393
Corbin, A. L. et al. IRF5 guides monocytes toward an inflammatory CD11c+ macrophage phenotype and promotes intestinal inflammation. Sci. Immunol. 5, 1–15 (2020).
doi: 10.1126/sciimmunol.aax6085
Persson, E. K., Scott, C. L., Mowat, A. M. & Agace, W. W. Dendritic cell subsets in the intestinal lamina propria: Ontogeny and function. Eur. J. Immunol. 43, 3098–3107. https://doi.org/10.1002/eji.201343740 (2013).
doi: 10.1002/eji.201343740
pubmed: 23966272
pmcid: 3933733
Schridde, A. et al. Tissue-specific differentiation of colonic macrophages requires TGFbeta receptor-mediated signaling. Mucosal. Immunol. 10, 1387–1399. https://doi.org/10.1038/mi.2016.142 (2017).
doi: 10.1038/mi.2016.142
pubmed: 28145440
pmcid: 5417360
Soehnlein, O., Lindbom, L. & Weber, C. Mechanisms underlying neutrophil-mediated monocyte recruitment. Blood 114, 4613–4623. https://doi.org/10.1182/blood-2009-06-221630 (2009).
doi: 10.1182/blood-2009-06-221630
pubmed: 19696199
Nakata, K., Yamamoto, M., Inagawa, H. & Soma, G. Effects of interactions between intestinal microbiota and intestinal macrophages on health. Anticancer Res. 33, 2849–2854 (2013).
pubmed: 23780969
Troy, A. E. et al. IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and limits intestinal inflammation in a murine model of colitis. J. Immunol. 183, 2037–2044. https://doi.org/10.4049/jimmunol.0802918 (2009).
doi: 10.4049/jimmunol.0802918
pubmed: 19596985
Shaw, T. N. et al. Tissue-resident macrophages in the intestine are long lived and defined by Tim-4 and CD4 expression. J. Exp. Med. 215, 1507–1518. https://doi.org/10.1084/jem.20180019 (2018).
doi: 10.1084/jem.20180019
pubmed: 29789388
pmcid: 5987925
Bain, C. C. & Schridde, A. Origin, differentiation, and function of intestinal macrophages. Front. Immunol. 9, 2733. https://doi.org/10.3389/fimmu.2018.02733 (2018).
doi: 10.3389/fimmu.2018.02733
pubmed: 30538701
pmcid: 6277706
Baghdadi, M. et al. TIM-4 glycoprotein-mediated degradation of dying tumor cells by autophagy leads to reduced antigen presentation and increased immune tolerance. Immunity 39, 1070–1081. https://doi.org/10.1016/j.immuni.2013.09.014 (2013).
doi: 10.1016/j.immuni.2013.09.014
pubmed: 24315994
Orecchioni, M., Ghosheh, Y., Pramod, A. B. & Ley, K. Macrophage polarization: Different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front Immunol 10, 1084. https://doi.org/10.3389/fimmu.2019.01084 (2019).
doi: 10.3389/fimmu.2019.01084
pubmed: 31178859
pmcid: 6543837
Coskun, M. Intestinal epithelium in inflammatory bowel disease. Front. Med. (Lausanne) 1, 24. https://doi.org/10.3389/fmed.2014.00024 (2014).
doi: 10.3389/fmed.2014.00024
pubmed: 25593900
Schreurs, M. W. J., Eggert, A. A. O., de Boer, A. J., Figdor, C. G. & Adema, G. J. Generation and functional characterization of mouse monocyte-derived dendritic cells. Eur. J. Immunol. 29, 2835–2841. https://doi.org/10.1002/(sici)1521-4141(199909)29:09%3c2835::Aid-immu2835%3e3.0.Co;2-q (1999).
doi: 10.1002/(sici)1521-4141(199909)29:09<2835::Aid-immu2835>3.0.Co;2-q
pubmed: 10508258
Li, N. et al. Serotonin activates dendritic cell function in the context of gut inflammation. Am. J. Pathol. 178, 662–671. https://doi.org/10.1016/j.ajpath.2010.10.028 (2011).
doi: 10.1016/j.ajpath.2010.10.028
pubmed: 21281798
pmcid: 3069907
Bain, C. C. et al. TGFbetaR signalling controls CD103(+)CD11b(+) dendritic cell development in the intestine. Nat. Commun. 8, 620. https://doi.org/10.1038/s41467-017-00658-6 (2017).
doi: 10.1038/s41467-017-00658-6
pubmed: 28931816
pmcid: 5607002
Stagg, A. J. Intestinal dendritic cells in health and gut inflammation. Front. Immunol. 9, 2883. https://doi.org/10.3389/fimmu.2018.02883 (2018).
doi: 10.3389/fimmu.2018.02883
pubmed: 30574151
pmcid: 6291504
Li, L. J. et al. Induction of colitis in mice with food allergen-specific immune response. Sci. Rep. 6, 32765. https://doi.org/10.1038/srep32765 (2016).
doi: 10.1038/srep32765
pubmed: 27604348
pmcid: 5015191
Yang, P. C. et al. TIM-4 expressed by mucosal dendritic cells plays a critical role in food antigen-specific Th2 differentiation and intestinal allergy. Gastroenterology 133, 1522–1533. https://doi.org/10.1053/j.gastro.2007.08.006 (2007).
doi: 10.1053/j.gastro.2007.08.006
pubmed: 17915221