Eosinophils Promote Generation and Maintenance of Immunoglobulin-A-Expressing Plasma Cells and Contribute to Gut Immune Homeostasis

•Eosinophils are required for development of mucosal IgA plasma cells•Eosinophils are required for the maintenance of mucosal plasma cells•In the absence of eosinophils, Tfh cell function in Peyer’s patches is abberant•Lack of eosinophils affects Treg and DC development in gut-associated tissues

SummaryAlthough in normal lamina propria (LP) large numbers of eosinophils are present, little is known about their role in mucosal immunity at steady state. Here we show that eosinophils are needed to maintain immune homeostasis in gut-associated tissues. By using eosinophil-deficient ΔdblGATA-1 and PHIL mice or an eosinophil-specific depletion model, we found a reduction in immunoglobulin A+ (IgA+) plasma cell numbers and in secreted IgA. Eosinophil-deficient mice also showed defects in the intestinal mucous shield and alterations in microbiota composition in the gut lumen. In addition, TGF-β-dependent events including class switching to IgA in Peyer’s patches (PP), the formation of CD103+ T cells including Foxp3+ regulatory (Treg), and also CD103+ dendritic cells were disturbed. In vitro cultures showed that eosinophils produce factors that promote T-independent IgA class switching. Our findings show that eosinophils are important players for immune homeostasis in gut-associated tissues and add to data suggesting that eosinophils can promote tissue integrity.

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