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.

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