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

C Gil-Cruz, C Perez-Shibayama, L Onder, Q Chai… - Nature …, 2016 - nature.com
C Gil-Cruz, C Perez-Shibayama, L Onder, Q Chai, J Cupovic, HW Cheng, M Novkovic
Nature immunology, 2016nature.com
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 …
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.
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