Regulatory T cells induced by B cells suppress NLRP3 inflammasome activation and alleviate monosodium urate-induced gouty inflammation

Summary: Regulatory T cells induced by B cells (Treg-of-B cells), a distinct Foxp3- Treg cell subset, have established the roles in the suppression of inflammatory conditions, including asthma and intestinal inflammation. However, little is known about the regulatory effects of Treg-of-B cells on innate immunity. Herein, we examined whether Treg-of-B cells could regulate macrophage function and prevent NLRP3-associated diseases, particularly inflammatory gouty arthritis. Treg-of-B cells, but not thymus-derived Treg or effector T cells, inhibited inflammasome-mediated IL-1β secretion, caspase-1 activation, and NLRP3 production by LPS/ATP stimulation in a cell contact-dependent manner. In addition, Treg-of-B cells inhibited monosodium urate-induced NLRP3 inflammasome activation in vitro via NF-κB signaling. Treg-of-B cells ameliorated gouty inflammation in a mouse air pouch model by reducing neutrophil and leukocyte influx and cytokine and chemokine production. Our results demonstrated that Treg-of-B cells exerted regulatory effects on innate immunity by suppressing NLRP3 inflammasome activation and feasible for future therapeutic applications.