Journal
NATURE IMMUNOLOGY
Volume 17, Issue 12, Pages 1388-1396Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3566
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Funding
- Swiss National Science Foundation [146133, 141918, 151370]
- Promedica Foundation
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [25460589, 16H05172, 15H01153]
- German Research Council [SFB974, GRK1949]
- Japanese Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [25460589, 24111001, 15H01153, 15F15114, 16K15288, 16H05172] Funding Source: KAKEN
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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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