Huang Jing-Hui, Chiang Bor-Luen
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
Department of Pediatrics, National Taiwan University Hospital, Taipei 10041, Taiwan.
iScience. 2021 Jan 29;24(2):102103. doi: 10.1016/j.isci.2021.102103. eCollection 2021 Feb 19.
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 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.
由B细胞诱导产生的调节性T细胞（B细胞来源的调节性T细胞）是一种独特的Foxp3调节性T细胞亚群，已被证实其在抑制包括哮喘和肠道炎症在内的炎症性疾病中发挥作用。然而，关于B细胞来源的调节性T细胞对固有免疫的调节作用却知之甚少。在此，我们研究了B细胞来源的调节性T细胞是否能够调节巨噬细胞功能并预防与NLRP3相关的疾病，尤其是炎症性痛风性关节炎。B细胞来源的调节性T细胞，而非胸腺来源的调节性T细胞或效应T细胞，以细胞接触依赖的方式抑制了脂多糖/三磷酸腺苷刺激引起的炎性小体介导的白细胞介素-1β分泌、半胱天冬酶-1激活及NLRP3生成。此外，B细胞来源的调节性T细胞通过核因子-κB信号通路抑制尿酸钠诱导的NLRP3炎性小体激活。在小鼠气袋模型中，B细胞来源的调节性T细胞通过减少中性粒细胞和白细胞流入以及细胞因子和趋化因子生成来改善痛风性炎症。我们的研究结果表明，B细胞来源的调节性T细胞通过抑制NLRP3炎性小体激活对固有免疫发挥调节作用，且在未来治疗应用中具有可行性。
