8^th European Immunology Conference

Biography

Biography: Liwei Lu

Abstract

Activation of autoreactive B cells leads to plasma cell (PC) formation and autoantibody production, contributing to the development of autoimmune diseases. Increasing evidence indicates a crucial role of leptin in immune response and autoimmune pathogenesis via enhancing CD4⁺ T cell responses, but whether and how leptin regulates B cell response in autoimmune pathogenesis remain largely unclear. Using collagen-induced arthritis (CIA) mice, we detected increased levels of leptin and anti-collagen II (CII) antibodies in the synovial fluid (SF) and sera of mice at acute and chronic stages of CIA. Higher percentage and cell number of PCs were observed in the SF of CIA mice. Leptin receptor-deficient (db/db) mice exhibited ameliorated CIA development with reduced PCs responses and CII-specific antibody production. Intra-articular injection of recombinant leptin enhanced PCs responses and CII-specific antibody production and joint damage. Importantly, intra-articular injection of a soluble leptin blocker (ObR:Fc) deceased PCs responses, CII-specific antibody production and joint damage. Mechanistic studies revealed that leptin promoted CD138⁺IFR4⁺ PC generation from GL-7⁺Fas⁺ germinal center B cells via activating Akt-mTOR-IRF4 axis. Moreover, .rapamycin treatment attenuated leptin-induced IRF4 expression and PCs generation. In RA patients, leptin levels and autoantibody production were positively correlated with disease activity (DAS28 score) with increased CD38⁺CD27⁺ plasmablasts detected in the synovium of active RA patients. Together, these findings demonstrated a critical role of leptin in enhancing PCs responses and CIA progression via ObR-Akt-mTOR-IRF4 axis, indicating that leptin blockade may serve as a potential therapeutic strategy for the treatment of autoimmune arthritis.