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 1β (IL-1β), inducible nitric oxide synthase, lymphotoxin (LT) α, and LT-β, and reduced levels of retinoic acid-related orphan receptor gamma t-positive (ROR-γt +) 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-β (transforming growth factor β). GI eosinophils expressed a relatively high level of IL-1β, and IL-1β-deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA + cells and ROR-γt + 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-1β in the small intestine.
Bibliographical noteFunding Information:
We thank the Cincinnati Digestive Health Center (P30 DK078392) Integrative Morphology Core for tissue processing, sectioning, histology, and immunohistochemical staining. We also thank Shawna Hottinger for editorial assistance. This work was supported by the NIH grants R37 AI045898 and R01 AI083450, the CURED (Campaign Urging Research for Eosinophilic Disease) Foundation, the Food Allergy Research & Education (FARE), and Buckeye Foundation. Y.J. was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2013R1A1A2004820). M.H.J. was supported by the Institute for Basic Science (IBS), Republic of Korea.