IL-1? in eosinophil-mediated small intestinal homeostasis and IgA production.

ABSTRACT: Eosinophils are multifunctional leukocytes that reside in the gastrointestinal (GI) lamina propria, where their basal function remains largely unexplored. In this study, by examining mice with a selective deficiency of systemic eosinophils (by lineage ablation) or GI eosinophils (eotaxin-1/2 double deficient or CC chemokine receptor 3 deficient), we show that eosinophils support immunoglobulin A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal microbial composition, and promote the development of Peyer's patches. Eosinophil-deficient mice showed reduced expression of mediators of secretory IgA production, including intestinal interleukin 1? (IL-1?), inducible nitric oxide synthase, lymphotoxin (LT) ?, and LT-?, and reduced levels of retinoic acid-related orphan receptor gamma t-positive (ROR-?t(+)) innate lymphoid cells (ILCs), while maintaining normal levels of APRIL (a proliferation-inducing ligand), BAFF (B cell-activating factor of the tumor necrosis factor family), and TGF-? (transforming growth factor ?). GI eosinophils expressed a relatively high level of IL-1?, and IL-1?-deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA(+) cells and ROR-?t(+) ILCs. On the basis of these collective data, we propose that eosinophils are required for homeostatic intestinal immune responses including IgA production and that their affect is mediated via IL-1? in the small intestine.

SUBMITTER: Jung Y 

PROVIDER: S-EPMC4481137 | biostudies-other | 2015 Jul

REPOSITORIES: biostudies-other