Tofacitinib treatment of rheumatoid arthritis increases senescent T cell frequency in patients and limits T cell function in vitro.

Autor: Alamino VA; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina.; Laboratorio de Inmunología, Hospital Nacional de Clínicas, UNC, Córdoba, Argentina., Onofrio LI; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina.; Laboratorio de Inmunología, Hospital Nacional de Clínicas, UNC, Córdoba, Argentina., Acosta CDV; Laboratorio de Inmunología, Hospital Nacional de Clínicas, UNC, Córdoba, Argentina., Ferrero PV; Laboratorio de Inmunología, Hospital Nacional de Clínicas, UNC, Córdoba, Argentina., Zacca ER; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina.; Laboratorio de Inmunología, Hospital Nacional de Clínicas, UNC, Córdoba, Argentina., Cadile II; Servicio de Reumatología, Hospital Nacional de Clínicas, UNC, Córdoba, Argentina., Mussano ED; Servicio de Reumatología, Hospital Nacional de Clínicas, UNC, Córdoba, Argentina., Onetti LB; Servicio de Reumatología, Hospital Nacional de Clínicas, UNC, Córdoba, Argentina., Montes CL; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina., Gruppi A; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina., Acosta Rodriguez EV; Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2023 Aug; Vol. 53 (8), pp. e2250353. Date of Electronic Publication: 2023 May 31.
DOI: 10.1002/eji.202250353
Abstrakt: 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.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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