HMGB1 exacerbates experimental mouse colitis by enhancing innate lymphoid cells 3 inflammatory responses via promoted IL-23 production.

摘要: In inflammatory bowel diseases (IBD), high mobility group box 1 (HMGB1), as an endogenous molecule, can promote cytokines secretion by acting on TLR2/4 resulting in tissue damage. The underlying mechanisms remain unclear. Here we report a novel role of HMGB1 controlling the maintenance and function intestine-resident group-3 innate lymphoid cells (ILC3s) that are important effector implicated mucosal homeostasis IBD pathogenesis. We showed mice treated with anti-HMGB1 Ab, or genetically deficient for TLR2-/- TLR4-/- mice, displayed reduced intestinal inflammation. these numbers colonic ILC3s were significantly reduced, levels IL-17 IL-22 be secreted also decreased colon tissues. Furthermore, promoted DCs via signaling to produce IL-23, activating IL-22. Our data thus indicated HMGB1-TLR2/4-DCs-IL-23 cascade pathway enhances functions IL-22, this signal way might play vital development IBD.