托法替尼
效应器
免疫衰老
CD8型
类风湿性关节炎
免疫系统
免疫学
生物
T细胞
细胞毒性T细胞
体外
遗传学
作者
Vanina Alejandra Alamino,Luisina I. Onofrio,Cristina Acosta,Paula Gallego Ferrero,Estefanía Zacca,Isaac Cadile,Eduardo Mussano,Laura Onetti,Carolina L. Montes,Adriana Gruppi,Eva V. Acosta Rodríguez
标识
DOI:10.1002/eji.202250353
摘要
Abstract Unraveling the immune signatures in rheumatoid arthritis (RA) patients receiving various treatment regimens can aid in comprehending the immune mechanisms’ role in treatment efficacy and side effects. Given the critical role of cellular immunity in RA pathogenesis, we sought to identify T‐cell profiles characterizing RA patients under specific treatments. We compared 75 immunophenotypic and biochemical variables in healthy donors (HD) and RA patients, including those receiving different treatments as well as treatment‐free patients. Additionally, we conducted in vitro experiments to evaluate the direct effect of tofacitinib on purified naïve and memory CD4 + and CD8 + T cells. Multivariate analysis revealed that tofacitinib‐treated patients segregated from HD at the expense of T‐cell activation, differentiation, and effector function‐related variables. Additionally, tofacitinib led to an accumulation of peripheral senescent memory CD4 + and CD8 + T cells. In vitro, tofacitinib impaired the activation, proliferation, and effector molecules expression and triggered senescence pathways in T‐cell subsets upon TCR‐engagement, with the most significant impact on memory CD8 + T cells. Our findings suggest that tofacitinib may activate immunosenescence pathways while simultaneously inhibiting effector functions in T cells, both effects likely contributing to the high clinical success and reported side effects of this JAK inhibitor in RA.
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