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

Abstract

Although 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.

Lung-resident eosinophils represent a distinct regulatory eosinophil subset

“…iEos showed higher In fact, under baseline conditions, eosinophils rapidly leave the bloodstream to enter tissues, mainly the gastrointestinal tract, adipose tissue, thymus, uterus, and mammary glands, where they regulate a variety of important biological functions (1,2,8,16). The vast majority of these tissue-resident eosinophils (rEos) are found in the nonesophageal portions of the gastrointestinal tract, where they promote IgA class switching and the maintenance of IgA-expressing plasma cells (17,18). They also support the development of Peyer's patches and mucus production in the small intestine (18).…”

Immunity to gastrointestinal nematode infections

“…Thus, despite being redundant for the expulsion of most nematodes, eosinophils might be important for wound healing and tissue regeneration in which they have been implicated in nonmucosal tissues. [194][195][196] Eosinophils have also been shown to promote the survival of long-lived plasma cells in the bone marrow 197 as well as the generation of IgA-secreting plasma cells in the gastrointestinal tract 179,198 (at least in the small intestine 199 ) via the production of IL-1b, suggesting that they might affect secondary challenge infections where antibodies presumably play a larger role. Indeed, both IL-5 and eosinophildeficient mice harbor increased numbers of N. brasiliensis larvae after secondary infection, 89 with similar results during secondary T. spiralis infection.…”

“…Indeed, both IL-5 and eosinophildeficient mice harbor increased numbers of N. brasiliensis larvae after secondary infection, 89 with similar results during secondary T. spiralis infection. 200 Furthermore, eosinophils negatively regulate Th17 cells 201 and promote the expansion of regulatory T cells in the steady state 198,202 that might affect overall inflammation, illustrating their complex contribution to tissue homeostasis. Similarly, whereas resident intestinal macrophages are mostly suppressive in nature and do not act inflammatory to pathogen stimulation, type 2 cytokines give rise to alternatively activated macrophages that might contribute to the expulsion of certain parasites.…”

Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB–induced Bcl-xL for inhibition of apoptosis

“…They are multifaceted cells of the innate immune system and generally associated with type 2 immune responses against allergens and helminths whereby they mediate proinflammatory and protective functions, respectively. Moreover, eosinophils were reported to support survival of plasma cells in the bone marrow, 1 promote differentiation of alternatively activated macrophages in fat tissue, 2,3 induce immunoglobulin A secretion in the gut, 4 and facilitate liver regeneration. 5 Eosinophils develop in the bone marrow from eosinophil lineagecommitted progenitors, which express the interleukin (IL)-5 receptor and the transcription factors Gata-1 and c/EBPa.…”