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

Publication

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

Journal Paper/Review - Oct 31, 2016

Gil Cruz Cristina, Scandella Elke, Ikuta Koichi, Cui Guangwei, Abe Shinya, McCoy Kathy D, Geuking Markus B, Lang Philipp A, Novkovic Mario, Cheng Hung-Wei, Cupovic Jovana, Chai Qian, Onder Lucas, Pérez Shibayama Christian Ivan, Ludewig Burkhard

Citation

Gil Cruz C, Scandella E, Ikuta K, Cui G, Abe S, McCoy K, Geuking M, Lang P, Novkovic M, Cheng H, Cupovic J, Chai Q, Onder L, Pérez Shibayama C, Ludewig B. Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs. Nat Immunol 2016; 17:1388-1396.

Type

Journal Paper/Review (English)

Journal

Nat Immunol 2016; 17

Publication Date

Oct 31, 2016

Issn Electronic

1529-2916

Pages

1388-1396

Brief description/objective

UNASSIGNED
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.