ILC-fibroblastic reticular cell interaction
Fibroblastic reticular cells (FRCs) of secondary lymphoid organs form distinct niches for interaction with hematopoietic cells. We found that IL-15 production by FRCs is essential for group 1 innate lymphoid cell (ILC1) maintenance in Peyer’s patches and mesenteric lymph nodes. Moreover, FRC-specific abrogation of myeloid differentiation primary response gene 88-dependent innate immune sensing unleashed IL-15 production by FRCs during enteropathogenic virus infection leading to hyperactivation of ILC1 and substantially altered T helper cell differentiation. Accelerated viral clearance by ILC1 precipitated severe intestinal inflammatory disease with commensal dysbiosis, loss of intestinal barrier function and reduced colonization resistance. In sum, FRCs act as “on-demand” immune rheostat by restraining ILC1 activation and thereby preventing immunopathological damage in the intestine.
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