Elsevier

Mucosal Immunology

Volume 8, Issue 4, July 2015, Pages 930-942
Mucosal Immunology

Article
IL-1β in eosinophil-mediated small intestinal homeostasis and IgA production

https://doi.org/10.1038/mi.2014.123Get rights and content
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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 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.

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Published online: 7 January 2015

SUPPLEMENTARY MATERIAL is linked to the online version of the paper

Supplementary information The online version of this article (doi:10.1038/mi.2014.123) contains supplementary material, which is available to authorized users.