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

Nat Immunol. 2016 Dec;17(12):1388-1396. doi: 10.1038/ni.3566. Epub 2016 Oct 31.

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.

MeSH terms

  • Animals
  • Cells, Cultured
  • Citrobacter rodentium / immunology*
  • Coronavirus Infections / immunology*
  • Enterobacteriaceae Infections / immunology*
  • Fibroblasts / immunology*
  • Immunity, Innate
  • Interleukin-15 / metabolism*
  • Lymph Nodes / pathology
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Murine hepatitis virus / immunology*
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Peyer's Patches / pathology
  • Th1 Cells / immunology
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / metabolism

Substances

  • Interleukin-15
  • Myeloid Differentiation Factor 88
  • TLR7 protein, human
  • Toll-Like Receptor 7