The JAK1/3 inhibitor tofacitinib regulates Th cell profiles and humoral immune responses in myasthenia gravis

Abstract

Abstract Background Tofacitinib, a first-generation Janus kinase (JAK) 1/3 inhibitor, is widely used in the treatment of ulcerative colitis and rheumatoid arthritis. However, its role in myasthenia gravis (MG) has not yet been clearly explored. Methods Here, we investigated the effects of tofacitinib on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. Besides, the effects of tofacitinib were studied in peripheral blood mononuclear cells (PBMCs) of patients with MG in vitro. Results The results revealed that tofacitinib administration ameliorated the severity of EAMG rats by restoring the balance of T helper type 1 (Th1)/Th2/Th17/Treg subsets and reducing the secretion of anti-acetylcholine receptor (AChR) antibodies by B cells. After treatment with tofacitinib in vitro, the percentage of Th1 cells and IgG-secreting B cells was significantly decreased, whereas regulatory T cells were significantly upregulated in mononuclear cells (MNCs) of EAMG rats, which were consistent with the results observed in PBMCs of MG patients. Furthermore, tofacitinib might inhibit CD4+ T cells differentiated into Th1 through decreasing phosphorylated signal transducers and activator of transcription 1 (Stat1) but promoted Treg cell differentiation through increasing phosphorylated Stat5 in MNCs from EAMG rats in vitro. Conclusions We concluded that tofacitinib could regulate humoral immune responses and Th cell profiles in MG, thus providing a promising therapeutic candidate for MG treatment.