细胞生物学
树突状细胞
化学
细胞
生物
免疫学
免疫系统
生物化学
作者
Sigrid Bülow,Katharina U. Ederer,Jonas Maurice Holzinger,Lisa Zeller,Maren Caroline Frogner Werner,Martina Toelge,Christina Pfab,Steffen Hirsch,Franziska Göpferich,Andreas Hiergeist,Friederike Berberich‐Siebelt,André Gessner
出处
期刊:Cell Reports
[Elsevier]
日期:2024-03-01
卷期号:43 (3): 113929-113929
标识
DOI:10.1016/j.celrep.2024.113929
摘要
Summary
Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of lipopolysaccharide. Here, we define BPI as a potent activator of murine dendritic cells (DCs). As shown in GM-CSF-cultured, bone-marrow-derived cells (BMDCs), BPI induces a distinct stimulation profile including IL-2, IL-6, and tumor necrosis factor expression. Conventional DCs also respond to BPI, while M-CSF-cultivated or peritoneal lavage macrophages do not. Subsequent to BPI stimulation of BMDCs, CD4+ T cells predominantly secrete IL-22 and, when naive, preferentially differentiate into T helper 22 (Th22) cells. Congruent with the tissue-protective properties of IL-22 and along with impaired IL-22 induction, disease severity is significantly increased during dextran sodium sulfate-induced colitis in BPI-deficient mice. Importantly, physiological diversification of intestinal microbiota fosters BPI-dependent IL-22 induction in CD4+ T cells derived from mesenteric lymph nodes. In conclusion, BPI is a potent activator of DCs and consecutive Th22 cell differentiation with substantial relevance in intestinal homeostasis.
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