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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 6weeks 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. [Copyright &y& Elsevier]

Treg is essential to limit the extend and duration of the immune response, but its stability is still under debate. Here we demonstrate that IL-17-producing Treg cells (Th17-like cells) increased in peripheral blood of patients with Systemic Lupus Erythematosus (SLE). Notably, the Th17-like cells from patient with active SLE were characterized with some phenotype and function of Th17 cells. Upon stimulation, Helios-Foxp3 + CD4+ T cells decrease Foxp3 expression but increase expression of IL-17 and RORγt. Damage associated molecule pattern and inflammatory cytokines are important for induction of IL-17 expression in Treg cells. The Th17-like cells from patients with active SLE lose suppressive function and have robust response to stimulation of autoantigens. We also observed that the level of Th17-like cells in peripheral blood is closely associated with the clinical index of SLE. These findings suggest that instability of Treg plays a critical role in pathogenesis of autoimmune diseases. • IL-17-producing Treg cells upregulate in both patients with active SLE and spontaneous lupus model. • IL-17-producing Treg cell originates from Helio− Treg upon stimulation of HMGB1 and IL-6. • IL-17-producing Treg in patients with active SLE responds to autoantigen stimulation, and shows regulatory deficiency. [ABSTRACT FROM AUTHOR]