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The scientific article of August, 2023 [Updated]


- What Rheumatoid Arthritis is? -

🤕 Did you know that while our immune system is crucial for maintaining our health, it can sometimes turn into the worst enemy? This is particularly evident in autoimmune diseases like Rheumatoid Arthritis (RA).

🔬 Under normal conditions, immune cells such as neutrophils and lymphocytes patrol our bodies, seeking out harmful pathogens and foreign invaders. Yet, in some instances, they mistakenly target our own tissues. In patients with RA, the immune system attacks the joint linings, resulting in chronic painful inflammation that, over time, can damage both cartilage and bone. The intricacies of this disease's mechanisms remain elusive, emphasizing the importance of continued research and drug development to assist those affected.
💊 In the present study, scientists treated RA patients with a drug called "tofacitinib." This medication binds to key molecules on our immune cells (JAK-receptor), leading to two important outcomes:
💡 It disarms effector lymphocytes, typically responsible for joint attacks, by preventing their differentiation and activation.
💡 Tofacitinib induces "senescence" in Lymphocyte T memory cells, causing them to lose vital functionalities.
✅ These findings are undoubtedly exiting for RA research and future findings!

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.

Illustration requested by Dr. Eva Acosta, from CIBICI-CONICET, UNC. Published in European Journal of Immunology, Jul, 2023.

TO READ THE COMPLETE STUDY HERE