Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs.

Gil-Cruz, Cristina; Perez-Shibayama, Christian; Onder, Lucas; Chai, Qian; Cupovic, Jovana; Cheng, Hung-Wei; Novkovic, Mario; Lang, Philipp A; Geuking, Markus; McCoy, Kathleen; Abe, Shinya; Cui, Guangwei; Ikuta, Koichi; Scandella, Elke; Ludewig, Burkhard (2016). Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs. Nature immunology, 17(12), pp. 1388-1396. Macmillan Publishers Limited 10.1038/ni.3566

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Fibroblastic reticular cells (FRCs) of secondary lymphoid organs form distinct niches for interaction with hematopoietic cells. We found here that production of the cytokine IL-15 by FRCs was essential for the maintenance of group 1 innate lymphoid cells (ILCs) in Peyer's patches and mesenteric lymph nodes. Moreover, FRC-specific ablation of the innate immunological sensing adaptor MyD88 unleashed IL-15 production by FRCs during infection with an enteropathogenic virus, which led to hyperactivation of group 1 ILCs and substantially altered the differentiation of helper T cells. Accelerated clearance of virus by group 1 ILCs precipitated severe intestinal inflammatory disease with commensal dysbiosis, loss of intestinal barrier function and diminished resistance to colonization. In sum, FRCs act as an 'on-demand' immunological 'rheostat' by restraining activation of group 1 ILCs and thereby preventing immunopathological damage in the intestine.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

UniBE Contributor:

Geuking, Markus and McCoy, Kathleen

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1529-2908

Publisher:

Macmillan Publishers Limited

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

03 May 2017 10:27

Last Modified:

03 May 2017 10:27

Publisher DOI:

10.1038/ni.3566

PubMed ID:

27798617

BORIS DOI:

10.7892/boris.94422

URI:

https://boris.unibe.ch/id/eprint/94422

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