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

Journal Paper/Review - Oct 31, 2016

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Gil Cruz C, Perez Shibayama C, Onder L, Chai Q, Cupovic J, Cheng H, Novkovic M, Lang P, Geuking M, McCoy K, Abe S, Cui G, Ikuta K, Scandella E, Ludewig B. Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs. Nat Immunol 2016; 17:1388-1396.
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Journal Paper/Review (English)
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Nat Immunol 2016; 17
Publication Date
Oct 31, 2016
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1529-2916
Pages
1388-1396
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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.