Lipopolysaccharide mediated mast cells induce IL-10 producing regulatory T cells through the ICOSL/ICOS axis

Autor: Gang Cai, Weiwei Zhang, Xiaomeng Nie, Beiying Wu, Qian Shen, Huaizhou Wang, Qiang Li
Rok vydání: 2011
Předmět:
Zdroj: Clinical immunology (Orlando, Fla.). 142(3)
ISSN: 1521-7035
Popis: 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.
Databáze: OpenAIRE