title: 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.
authors.affiliation: Deutsches Rheuma Forschungszentrum Berlin, a Leibniz Institute, 10117 Berlin, Germany.
authors.forename: Van Trung
authors.initials: VT
authors.lastname: Chu
authors.affiliation: Deutsches Rheuma Forschungszentrum Berlin, a Leibniz Institute, 10117 Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Beller
authors.affiliation: Institut für Immunologie, Veterinärmedizin, Freie Universität Berlin, 14163 Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rausch
authors.affiliation: Institut für Immunologie, Veterinärmedizin, Freie Universität Berlin, 14163 Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Strandmark
authors.affiliation: Internal Medicine, Immanuel Klinikum Bernau, 16321 Bernau, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zänker
authors.affiliation: Institute for Transfusion Medicine, Universitätsmedizin Charité, 10117 Berlin, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Arbach
authors.affiliation: Deutsches Rheuma Forschungszentrum Berlin, a Leibniz Institute, 10117 Berlin, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Kruglov
authors.affiliation: Deutsches Rheuma Forschungszentrum Berlin, a Leibniz Institute, 10117 Berlin, Germany. Electronic address: berek@drfz.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Berek
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D006706:Homeostasis; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics; D039001:Integrin alpha Chains / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000235:genetics; D010581:Peyer's Patches / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007070:Immunoglobulin A; D039001:Integrin alpha Chains; C091367:alpha E integrins