title: Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs.
abstract: 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.
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Cristina
authors: C
authors: Gil-Cruz
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Christian
authors: C
authors: Perez-Shibayama
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Lucas
authors: L
authors: Onder
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Qian
authors: Q
authors: Chai
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Jovana
authors: J
authors: Cupovic
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Hung-Wei
authors: HW
authors: Cheng
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Mario
authors: M
authors: Novkovic
authors: Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
authors: Philipp A
authors: PA
authors: Lang
authors: Division of Gastroenterology, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors: Markus B
authors: MB
authors: Geuking
authors: Division of Gastroenterology, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors: Kathy D
authors: KD
authors: McCoy
authors: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.|Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Shinya
authors: S
authors: Abe
authors: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors: Guangwei
authors: G
authors: Cui
authors: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors: Koichi
authors: K
authors: Ikuta
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Elke
authors: E
authors: Scandella
authors: Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors: Burkhard
authors: B
authors: Ludewig
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D044082:Citrobacter rodentium / Q000276:immunology*; D018352:Coronavirus Infections / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology*; D007113:Immunity, Innate; D019409:Interleukin-15 / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D010581:Peyer's Patches / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism
chemical_list: D019409:Interleukin-15; D053594:Myeloid Differentiation Factor 88; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7