Artículo
Tofacitinib treatment of rheumatoid arthritis increases senescent T cell frequency in patients and limits T cell function in vitro
Alamino, Vanina Alejandra
; Onofrio, Luisina Inés
; Acosta, Cristina del Valle; Ferrero, Paola Virginia; Zacca, Estefanía
; Cadile, Isaac I.; Mussano, Eduardo Daniel Eugenio; Onetti, Laura Beatriz; Montes, Carolina Lucia
; Gruppi, Adriana
; Acosta Rodriguez, Eva Virginia
Fecha de publicación:
08/2023
Editorial:
Wiley VCH Verlag
Revista:
European Journal of Immunology
ISSN:
0014-2980
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
IMMUNOSENESCENCE
,
JAK INHIBITOR
,
RHEUMATOID ARTHRITIS
,
T CELLS
,
TOFACITINIB
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - CORDOBA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Alamino, Vanina Alejandra; Onofrio, Luisina Inés; Acosta, Cristina del Valle; Ferrero, Paola Virginia; Zacca, Estefanía; et al.; Tofacitinib treatment of rheumatoid arthritis increases senescent T cell frequency in patients and limits T cell function in vitro; Wiley VCH Verlag; European Journal of Immunology; 53; 8; 8-2023; 1-12
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