T cell dysregulation in rheumatoid arthritis: Recent advances and natural product interventions

Autoimmune diseases result from chronic and dysregulated activation of the immune system, culminating in pathological self-tissue damage. These disorders are primarily driven by adaptive immune responses, particularly those mediated by T and B lymphocytes, which mistakenly target self-antigens expressed in host tissues. In rheumatoid arthritis (RA), the pathogenesis is closely associated with the emergence of tissue-invasive effector T cells and the functional impairment of regulatory T cells (Tregs), both of which play pivotal roles in disease progression. Therapeutic interventions targeting these dysregulated T cell populations have emerged as a promising strategy for RA management. Although synthetic immunosuppressants remain the mainstay of RA treatment, their long-term application is often hampered by adverse effects, diminished therapeutic efficacy, and poor patient adherence. These limitations highlight the critical need for the development of novel therapeutic approaches. Natural compounds derived from medicinal plants have been widely utilized in the clinical management of RA, with growing evidence supporting their immunomodulatory potential, particularly in restoring T cell-mediated immune tolerance. This review aims to provide a comprehensive overview of recent advances in understanding T cell dysregulation in RA and to elucidate the mechanisms through which natural compounds regulate immune responses. By integrating current findings, this work seeks to offer a theoretical foundation for the optimized use of natural compounds in the treatment of RA, while exploring their potential in advancing precision medicine and personalized therapeutic strategies.