IL-1 beta 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 orCC 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 beta (IL-1 beta), inducible nitric oxide synthase, lymphotoxin (LT) alpha, and LT-beta, and reduced levels of retinoic acid-related orphan receptor gamma t-positive (ROR-gamma 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-beta (transforming growth factor beta). GI eosinophils expressed a relatively high level of IL-1 beta, and IL-1 beta-deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA(+) cells and ROR-gamma 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 beta in the small intestine.