Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 Feb 2024
Historique:
received: 20 04 2023
accepted: 09 02 2024
medline: 27 2 2024
pubmed: 27 2 2024
entrez: 26 2 2024
Statut: epublish

Résumé

Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA

Identifiants

pubmed: 38409190
doi: 10.1038/s41467-024-46076-3
pii: 10.1038/s41467-024-46076-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1752

Subventions

Organisme : Barncancerfonden (Swedish Childhood Cancer Foundation)
ID : 2021

Informations de copyright

© 2024. The Author(s).

Références

Davidson, S. et al. Fibroblasts as immune regulators in infection, inflammation and cancer. Nat. Rev. Immunol. 21, 704–717 (2021).
pubmed: 33911232
Koliaraki, V., Prados, A., Armaka, M. & Kollias, G. The mesenchymal context in inflammation, immunity and cancer. Nat. Immunol. 21, 974–982 (2020).
pubmed: 32747813
Greicius, G. et al. PDGFRα+ pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo. Proc. Natl Acad. Sci. USA 115, E3173–E3181 (2018).
pubmed: 29559533 pmcid: 5889626
Owens, B. M. J. et al. CD90(+) stromal cells are non-professional innate immune effectors of the human colonic mucosa. Front. Immunol. 4, 307 (2013).
pubmed: 24137162 pmcid: 3786311
McCarthy, N. et al. Distinct mesenchymal cell populations generate the essential intestinal BMP signaling gradient. Cell Stem Cell 26, 391–402.e5 (2020).
pubmed: 32084389 pmcid: 7412576
Kinchen, J. et al. Structural remodeling of the human colonic mesenchyme in inflammatory bowel disease. Cell 175, 372–386.e17 (2018).
pubmed: 30270042 pmcid: 6176871
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
Martin, J. C. et al. Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy. Cell 178, 1493–1508.e20 (2019).
pubmed: 31474370 pmcid: 7060942
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
Elmentaite, R. et al. Cells of the human intestinal tract mapped across space and time. Nature 597, 250–255 (2021).
pubmed: 34497389 pmcid: 8426186
Elmentaite, R. et al. Single-cell sequencing of developing human gut reveals transcriptional links to childhood Crohn’s disease. Dev. Cell https://doi.org/10.1016/j.devcel.2020.11.010 . (2020).
Korsunsky, I. et al. Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases. Medicines 3, 481–518.e14 (2022).
Jasso, G. J. et al. Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing. PLoS Biol. 20, e3001532 (2022).
pubmed: 35085231 pmcid: 8824371
West, N. R. et al. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease. Nat. Med. 23, 579–589 (2017).
pubmed: 28368383 pmcid: 5420447
Kvedaraite, E. Neutrophil—T cell crosstalk in inflammatory bowel disease. Immunology https://doi.org/10.1111/imm.13391 . (2021).
Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496–502 (2019).
pubmed: 30787437 pmcid: 6434952
Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902.e21 (2019).
pubmed: 31178118 pmcid: 6687398
Cromer, W. E., Mathis, J. M., Granger, D. N., Chaitanya, G. V. & Alexander, J. S. Role of the endothelium in inflammatory bowel diseases. World J. Gastroenterol. 17, 578–593 (2011).
pubmed: 21350707 pmcid: 3040330
Puré, E. & Cuff, C. A. A crucial role for CD44 in inflammation. Trends Mol. Med. 7, 213–221 (2001).
pubmed: 11325633
Nayar, S. et al. A myeloid–stromal niche and gp130 rescue in NOD2-driven Crohn’s disease. Nature. https://doi.org/10.1038/s41586-021-03484-5 (2021).
Graham, D. B. & Xavier, R. J. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature 578, 527–539 (2020).
pubmed: 32103191 pmcid: 7871366
Wei, K., Nguyen, H. N. & Brenner, M. B. Fibroblast pathology in inflammatory diseases. J. Clin. Invest. 131, e149538 (2021).
pubmed: 34651581 pmcid: 8516469
Parigi, S. M. et al. The spatial transcriptomic landscape of the healing mouse intestine following damage. Springer US https://doi.org/10.1038/s41467-022-28497-0 . (2022).
Czarnewski, P. et al. Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification. Nat. Commun. 10, 2892 (2019).
pubmed: 31253778 pmcid: 6598981
Frede, A. et al. B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing. Immunity 55, 2336–2351.e12 (2022).
pubmed: 36462502
Zhou, X. et al. Circuit design features of a stable two-cell system. Cell 172, 744–757.e17 (2018).
pubmed: 29398113 pmcid: 7377352
Dieckgraefe, B. K. & Korzenik, J. R. Treatment of active Crohn’s disease with recombinant human granulocyte-macrophage colony-stimulating factor. Lancet 360, 1478–1480 (2002).
pubmed: 12433518
Däbritz, J. Granulocyte macrophage colony-stimulating factor and the intestinal innate immune cell homeostasis in Crohn’s disease. Am. J. Physiol. 306, G455–G465 (2014).
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 (2014).
pubmed: 25151491 pmcid: 4169290
Liu, Z. et al. Fate mapping via Ms4a3-expression history traces monocyte-derived cells. Cell 178, 1509–1525.e19 (2019).
pubmed: 31491389
Sharma, A. et al. Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in hepatocellular carcinoma. Cell 183, 377–394.e21 (2020).
pubmed: 32976798
Mulder, K. et al. Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease. Immunity https://doi.org/10.1016/j.immuni.2021.07.007 . (2021).
Ramos, R. N. et al. Tissue-resident FOLR2+ macrophages associate with CD8+ T cell infiltration in human breast cancer. Cell 185, 1189–1207.e25 (2022).
Amorim, A. et al. IFNγ and GM-CSF control complementary differentiation programs in the monocyte-to-phagocyte transition during neuroinflammation. Nat. Immunol. 23, 217–228 (2022).
pubmed: 35102344
Menezes, S. et al. The heterogeneity of Ly6Chi monocytes controls their differentiation into iNOS+ macrophages or monocyte-derived dendritic cells. Immunity 45, 1205–1218 (2016).
pubmed: 28002729 pmcid: 5196026
Tan-Garcia, A. et al. Liver fibrosis and CD206+ macrophage accumulation are suppressed by anti-GM-CSF therapy. Jhep Rep. 2, 100062 (2020).
pubmed: 32039403
Guilliams, M. et al. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J. Exp. Med. 210, 1977–1992 (2013).
pubmed: 24043763 pmcid: 3782041
Schneider, C. et al. Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat. Immunol. 15, 1026–1037 (2014).
pubmed: 25263125
Becher, B., Tugues, S. & Greter, M. GM-CSF: from growth factor to central mediator of tissue inflammation. Immunity 45, 963–973 (2016).
pubmed: 27851925
Croxford, A. L. et al. The cytokine GM-CSF drives the inflammatory signature of CCR2+ monocytes and licenses autoimmunity. Immunity 43, 502–514 (2015).
pubmed: 26341401
Park, M. D., Silvin, A., Ginhoux, F. & Merad, M. Macrophages in health and disease. Cell 185, 4259–4279 (2022).
pubmed: 36368305 pmcid: 9908006
Evren, E. et al. Distinct developmental pathways from blood monocytes generate human lung macrophage diversity. Immunity https://doi.org/10.1016/j.immuni.2020.12.003 . (2020).
Egea, L., Hirata, Y. & Kagnoff, M. F. GM-CSF: a role in immune and inflammatory reactions in the intestine. Expert Rev. Gastroenterol. 4, 723–731 (2010).
Mortha, A. et al. Neutralizing anti-granulocyte macrophage-colony stimulating factor autoantibodies recognize post-translational glycosylations on granulocyte macrophage-colony stimulating factor years before diagnosis and predict complicated Crohn’s disease. Gastroenterology 163, 659–670 (2022).
pubmed: 35623454
Han, X. et al. Granulocyte-macrophage colony-stimulating factor autoantibodies in murine ileitis and progressive ileal Crohn’s disease. Gastroenterology 136, 1261–1271.e3 (2009).
pubmed: 19230854
Gathungu, G. et al. Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease. World J. Gastroenterol. 24, 623–630 (2018).
pubmed: 29434451 pmcid: 5799863
Denson, L. A. et al. Genetic and transcriptomic variation linked to neutrophil granulocyte-macrophage colony-stimulating factor signaling in pediatric Crohn’s disease. Inflamm. Bowel Dis. 25, 547–560 (2019).
pubmed: 30124884
Gathungu, G. et al. Granulocyte-macrophage colony-stimulating factor autoantibodies: a marker of aggressive Crohn’s disease. Inflamm. Bowel Dis. 19, 1671–80 (2013).
pubmed: 23749272
Ibraheim, H. et al. Systematic review with meta-analysis: effectiveness of anti-inflammatory therapy in immune checkpoint inhibitor-induced enterocolitis. Aliment Pharm. Ther. 52, 1432–1452 (2020).
Li, Y. et al. The prognostic and clinicopathological roles of PD-L1 expression in colorectal cancer: a systematic review and meta-analysis. Front. Pharm. 10, 139 (2019).
Cantero-Cid, R. et al. PD-L1/PD-1 crosstalk in colorectal cancer: are we targeting the right cells? BMC Cancer 18, 945–9 (2018).
pubmed: 30285662 pmcid: 6171318
Maier, B. et al. A conserved dendritic-cell regulatory program limits antitumour immunity. Nature 580, 257–262 (2020).
pubmed: 32269339 pmcid: 7787191
Ginhoux, F., Guilliams, M. & Merad, M. Expanding dendritic cell nomenclature in the single-cell era. Nat Rev Immunol 22, 67–68 (2021).
Kvedaraite, E. & Ginhoux, F. Human dendritic cells in cancer. Sci. Immunol. 7, eabm9409 (2022).
pubmed: 35363544
Kvedaraite, E. et al. Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology. Sci. Immunol. 7, eadd3330–eadd3330 (2022).
pubmed: 36525505 pmcid: 7614120
Danese, S. Role of the vascular and lymphatic endothelium in the pathogenesis of inflammatory bowel disease: ‘brothers in arms. Gut 60, 998 (2011).
pubmed: 21212253
Meizlish ML, Franklin RA, Zhou X, Medzhitov R. Tissue Homeostasis and Inflammation. Annu Rev Immunol. 39, 557–581 (2021).
Hyams, J. et al. Evaluation of the pediatric Crohn disease activity index: a prospective multicenter experience. J. Pediatr. Gastroenterol. Nutr. 41, 416–421 (2005).
pubmed: 16205508
Ludvigsson, J. F. et al. Swedish inflammatory bowel disease register (SWIBREG)—a nationwide quality register. Scand. J. Gastroenterol. 54, 1089–1101 (2019).
pubmed: 31498717
Schroeder, K. W., Tremaine, W. J. & Ilstrup, D. M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N. Engl. J. Med. 317, 1625–1629 (1987).
pubmed: 3317057
Kvedaraite, E. et al. Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD. Gut 65, 1632 (2021).
Fenton, T. M. et al. Immune profiling of human gut-associated lymphoid tissue identifies a role for isolated lymphoid follicles in priming of region-specific immunity. Immunity 52, 557–570.e6 (2020).
pubmed: 32160523 pmcid: 7155934
Kvedaraite, E. et al. Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity. Proc. Natl Acad. Sci. USA 118, e2018587118–12 (2021).
pubmed: 33479167 pmcid: 8017719
Becht, E. et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat. Biotechnol. 37, 38–44 (2018).
Levine, J. H. et al. Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis. Cell 162, 184–197 (2015).
pubmed: 26095251 pmcid: 4508757
Luecken, M. D. & Theis, F. J. Current best practices in single‐cell RNA‐seq analysis: a tutorial. Mol. Syst. Biol. 15, 360–23 (2019).
Dong, M. et al. SCDC: bulk gene expression deconvolution by multiple single-cell RNA sequencing references. Brief. Bioinform. 22, 416–427 (2020).
pmcid: 7820884
Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019).
pubmed: 31740819 pmcid: 6884693
McInnes, L., Healy, J. & Melville, J. UMAP: uniform manifold approximation and projection for dimension reduction. Preprint at arXiv https://doi.org/10.48550/arxiv.1802.03426 . (2018).
McInnes, L., Healy, J., Saul, N. & Großberger, L. UMAP: uniform manifold approximation and projection. J. Open Source Softw. 3, 861 (2018).
Lourda, M. et al. Detection of IL-17A-producing peripheral blood monocytes in Langerhans cell histiocytosis patients. Clin. Immunol. 153, 112–122 (2014).
pubmed: 24743018

Auteurs

Egle Kvedaraite (E)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. egle.kvedaraite@ki.se.
Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. egle.kvedaraite@ki.se.
Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden. egle.kvedaraite@ki.se.

Magda Lourda (M)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Natalia Mouratidou (N)

Pediatric Gastroenterology, Hepatology and Nutrition Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Tim Düking (T)

Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.

Avinash Padhi (A)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Dermatology and Venereology Section, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

Kirsten Moll (K)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Paulo Czarnewski (P)

Science for Life Laboratory, Department of Biochemistry and Biophysics and National Bioinformatics Infrastructure Sweden, Stockholm University, Solna, Sweden.

Indranil Sinha (I)

Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Ioanna Xagoraris (I)

Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Efthymia Kokkinou (E)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Anastasios Damdimopoulos (A)

Bioinformatics and Expression Analysis Core Facility, Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

Whitney Weigel (W)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Olga Hartwig (O)

Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.

Telma E Santos (TE)

Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.

Tea Soini (T)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Aline Van Acker (A)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Tech Watch, Flanders Institute for Biotechnology, Ghent, Belgium.

Nelly Rahkonen (N)

Integrated Cardio Metabolic Centre, Department of Medicine Huddinge, Karolinska Institutet, Huddinge, Sweden.

Malin Flodström Tullberg (M)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Emma Ringqvist (E)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Marcus Buggert (M)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Carl Jorns (C)

Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Ulrik Lindforss (U)

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Pelvic Cancer, GI Oncology and Colorectal Surgery Unit, Karolinska University Hospital, Stockholm, Sweden.

Caroline Nordenvall (C)

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Pelvic Cancer, GI Oncology and Colorectal Surgery Unit, Karolinska University Hospital, Stockholm, Sweden.

Christopher T Stamper (CT)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

David Unnersjö-Jess (D)

Science for Life Laboratory, Dept. of Applied Physics, Royal Institute of Technology, Solna, Sweden.

Mira Akber (M)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Ruta Nadisauskaite (R)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Jessica Jansson (J)

Pediatric Gastroenterology, Hepatology and Nutrition Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

Niels Vandamme (N)

VIB Single Cell Core, VIB, Ghent, Belgium.
VIB-UGent Center for Inflammation Research, 9052, Ghent, Belgium.

Chiara Sorini (C)

Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden.

Marijke Elise Grundeken (ME)

Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

Helena Rolandsdotter (H)

Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Sachs' Children and Youth Hospital, Department of Gastroenterology, Södersjukhuset, Stockholm, Sweden.

George Rassidakis (G)

Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Eduardo J Villablanca (EJ)

Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden.

Maja Ideström (M)

Pediatric Gastroenterology, Hepatology and Nutrition Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Stefan Eulitz (S)

Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.

Henrik Arnell (H)

Pediatric Gastroenterology, Hepatology and Nutrition Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Jenny Mjösberg (J)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Jan-Inge Henter (JI)

Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Theme of Children's Health, Karolinska University Hospital, Stockholm, Sweden.

Mattias Svensson (M)

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. mattias.svensson@ki.se.

Classifications MeSH