title: Lipopolysaccharide mediated mast cells induce IL-10 producing regulatory T cells through the ICOSL/ICOS axis.
abstract: The mechanisms by which mast cells (MCs) regulate immune responses are still largely unknown. Here, we showed that MCs induced interleukin (IL)-10 producing T cells to regulate inflammatory responses. To gain insight into the molecules involved, we set up an in vitro system in which lipopolysaccharide (LPS) stimulated MCs and CD4(+) T cells were co-cultured. Induction of IL-10 producing regulatory T cells mainly relied on the inducible costimulator ligand (ICOSL)/ICOS axis. MCs stimulated with LPS for more than 6 weeks upregulated ICOSL expression, while icosl(-/-) BMMCs failed to induce IL-10 producing T cells. The LPS effect was mediated through NF-κB activation via the TLR4 signaling pathway. Ex vivo analysis of bronchoalveolar lavage fluid from mice with LPS-mediated pneumonia revealed ICOSL(+) MCs and IL-10 producing T cell induction. Additionally, adaptive transfer of ICOSL(+) BMMCs attenuated LPS-mediated inflammation in MC-deficient mice. This study provided new evidence for the regulatory role of MCs.
authors.affiliation: Department of Respiratory Diseases, Changhai Hospital, the Second Military Medical University, Shanghai, PR China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Nie
authors.forename: Gang
authors.initials: G
authors.lastname: Cai
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.forename: Huaizhou
authors.initials: H
authors.lastname: Wang
authors.forename: Beiying
authors.initials: B
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10