Low-dose IL-2 Ameliorates Experimental Autoimmune Myasthenia Gravis in Rats by Restoring the CD4-positive Helper T-cell Balance Via the JAK/STAT5 Pathway.

Myasthenia gravis (MG) represents a prototypical autoimmune disorder that targets neuromuscular junctions. Emerging insights into the pathogenic role of cellular immunity in MG have intensified investigations of potential immunomodulatory therapies, and low-dose interleukin-2 (LD-IL-2) has garnered particular attention because of its ability to restore immune balance, maintain immune homeostasis, and ensure immune tolerance. To systematically investigate the therapeutic potential of LD-IL-2 in MG and elucidate its underlying mechanisms, we established an experimental autoimmune myasthenia gravis (EAMG) rat model to assess its therapeutic effects on clinical manifestations and CD4-positive helper T (CD4+ T) cell subset differentiation. Through integrated in vivo and in vitro experiments, we conducted a comprehensive evaluation of the immunoregulatory properties of LD-IL-2 in the context of EAMG pathogenesis. Our results revealed a pronounced imbalance in CD4+ T cells in EAMG model rats. Our research confirmed that LD-IL-2 might restore the Th17/regulatory T (Treg) cell and T follicular helper (Tfh)/T follicular regulatory (Tfr) cell ratios, thereby reestablishing the balance of CD4+ T cells in the EAMG model and improving the clinical severity of EAMG in rats. Moreover, we demonstrated that LD-IL-2 might exert its effects by activating the JAK1/JAK3/STAT5 signaling pathway and modulating CD4+ T cell differentiation. Collectively, our research provides compelling evidence supporting LD-IL-2 as a viable immunotherapeutic candidate for MG, laying a robust experimental foundation for future clinical applications in MG patients.