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

Abstract

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.

Polysaccharide extract from Isatidis Radix inhibits multiple inflammasomes activation and alleviate gouty arthritis

“…Gout is the most universal inflammatory arthritis in men older than 40 years, with an incidence of 4.0 in men and 1.4 in women per 1,000 person (Roddy & Choi, 2014). The pathogenesis of MSU is readily phagocytosed by macrophages and then macrophages acquire a proinflammatory M1 phenotype and release a large number of proinflammatory factors, such as IL‐1β, IL‐6 and TNF‐α, which induce a comprehensive inflammation storm through recruitment of neutrophils (J. H. Huang & Chiang, 2021).…”

B cell-T cell interplay in immune regulation: A focus on follicular regulatory T and regulatory B cell functions

“…LAG3 and CTLA4 are also important for Treg-of-B cells to exert inhibitory effect (Chen et al, 2016;. In mice with monosodium urate (MSU)induced gout, Treg-of-B cells migrate into draining lymph nodes to mitigate arthritis through repressing NLR family pyrin domain containing 3(NLRP3)-related inflammation triggered by macrophages (Huang and Chiang, 2021). NLRP3 inflammasome is a multi-protein complex and its activation involves two steps.…”

“…Step two is that Adenosine Triphosphate (ATP) or MSU crystals result in NLRP3 inflammasome assembly which then binds to caspase-1 to induce the delivery of IL-1β (Aizawa et al, 2020). Treg-of-B cells inhibit NF-kB pathways of macrophages via cell:cell contact, which culminates in the suppression of IL-1β generation from macrophages (Huang and Chiang, 2021). In general, the molecules mediating Tregof-B cells, regulatory mechanisms remain to be investigated.…”

Attenuation of the severity and changes in the microbiota in an animal model of primary biliary cholangitis by FOXP3− regulatory T cells

“…Treatment with LAG3 high Treg/B cells ameliorated joint inflammation and clinical symptoms in collagen‐induced arthritis mice 28 . Treg/B cells repressed NLRP3 inflammasome activation and attenuated gouty inflammation in a murine air pouch model 29 . However, the detailed mechanisms and applications of Treg/B cells in autoimmune liver diseases have not been elucidated.…”

“…28 Treg/B cells repressed NLRP3 inflammasome activation and attenuated gouty inflammation in a murine air pouch model. 29 However, the detailed mechanisms and applications of Treg/B cells in autoimmune liver diseases have not been elucidated.…”