Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs
Journal Paper/Review - Oct 31, 2016
Gil Cruz Cristina, Perez Shibayama Christian, Onder Lucas, Chai Qian, Cupovic Jovana, Cheng Hung-Wei, Novkovic Mario, Lang Philipp A, Geuking Markus B, McCoy Kathy D, Abe Shinya, Cui Guangwei, Ikuta Koichi, Scandella Elke, Ludewig Burkhard
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.