Maternal Immunoglobulin A regulates the development of the neonatal microbiota and intestinal microbiota-specific CD4+ T cell responses
Maternal Immunoglobulin A regulates the development of the neonatal microbiota and intestinal microbiota-specific CD4+ T cell responses
Abstract Breast milk is a complex mixture of nutrients and bioactives that promote infant development and decrease the incidence of chronic inflammatory disease. We investigated the role of one milk-derived bioactive, Immunoglobulin A (IgA) on the developing small intestinal microbiota and immune system. We demonstrate that early in life, milk-derived IgA suppressed colonization of the small intestine by Enterobacteriaceae and regulated the maturation of the small intestinal epithelium and the development of intestinal IL-17-producing CD4+ T cells. Enterobacteriaceae- specific CD4+ T cells, induced in the first weeks of life in the absence of milk-derived IgA, persisted in the intestine as memory T cells that can contribute to inflammatory disease later in life. Our study suggests that milk-derived IgA shapes mucosal immunity by regulating the neonatal microbiota thus preventing the development of long-lived intestinal microbiota-specific T cells.
Deschepper Jacob D.、Poholek Amanda C.、Fabre Shelcie、Yang Aaron、Hand Timothy W.、Rai Ali T.、Cai Yixuan、Frazer Austin J.、Abbott Darryl A.
University of Pittsburgh Gnotobiotic Core Facility, University of Pittsburgh School of MedicineDepartment of Immunology, University of Pittsburgh School of Medicine||Department of Pediatrics, University of Pittsburgh School of Medicine||UPMC Children?ˉs Hospital of PittsburghDepartment of Pediatrics, University of Pittsburgh School of Medicine||UPMC Children?ˉs Hospital of PittsburghDepartment of Immunology, University of Pittsburgh School of MedicineDepartment of Immunology, University of Pittsburgh School of Medicine||Department of Pediatrics, University of Pittsburgh School of Medicine||UPMC Children?ˉs Hospital of PittsburghDepartment of Pediatrics, University of Pittsburgh School of Medicine||UPMC Children?ˉs Hospital of PittsburghDepartment of Pediatrics, University of Pittsburgh School of Medicine||UPMC Children?ˉs Hospital of PittsburghDepartment of Pediatrics, University of Pittsburgh School of Medicine||UPMC Children?ˉs Hospital of PittsburghDepartment of Immunology, University of Pittsburgh School of Medicine
基础医学预防医学微生物学
Deschepper Jacob D.,Poholek Amanda C.,Fabre Shelcie,Yang Aaron,Hand Timothy W.,Rai Ali T.,Cai Yixuan,Frazer Austin J.,Abbott Darryl A..Maternal Immunoglobulin A regulates the development of the neonatal microbiota and intestinal microbiota-specific CD4+ T cell responses[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2024.06.10.598156.点此复制
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