2. Academic Validation
  3. Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs

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.
Cristina Gil-Cruz 1,  Christian Perez-Shibayama 1,  Lucas Onder 1,  Qian Chai 1,  Jovana Cupovic 1,  Hung-Wei Cheng 1,  Mario Novkovic 1,  Philipp A Lang 2,  Markus B Geuking 3,  Kathy D McCoy 3,  Shinya Abe 4 5,  Guangwei Cui 4,  Koichi Ikuta 4,  Elke Scandella 1,  Burkhard Ludewig 1
Affiliations

Affiliations

  • 1 Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • 2 Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
  • 3 Division of Gastroenterology, Department of Clinical Research, University of Bern, Bern, Switzerland.
  • 4 Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, Japan.
  • 5 Graduate School of Medicine, Kyoto University, Kyoto, Japan.
PMID: 27798617 DOI: 10.1038/ni.3566
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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