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

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.

► Long-term LPS stimulated BMMCs increased ICOSL expression in TLR4 dependent manner. ► ICOSL expressing BMMCs induce production of IL-10 producing cells in vitro. ► ICOSL+ BMMCs attenuated pneumonia through induction of IL-10 producing cells in vivo.