Sorafenib inhibits multiple sclerosis by regulating T cell differentiation

Abstract

Multiple sclerosis (MS) is a group of disorder characterized by aberrant T cell reactivity toward self-antigens with loss of immunological tolerance, resulting in chronic inflammation and tissue damage. CD4⁺ Th cells can differentiate into Th1, Th2, Th17, and Treg cells in response to a specific class of pathogenic microorganisms and to the cytokine milieu. Here, we found that tyrosine kinase inhibitor sorafenib (Sora), which had been approved by FDA for the treatment of tumor, could suppress pro-inflammatory Th1, Th17 cell differentiation, and promote anti-inflammatory Treg cell polarization. Furthermore, Sora suppressed Th1 and Th17 cell differentiation by STAT4 and TGF-β1 signaling, respectively. In addition, treatment with Sora in mice inhibited Th1, Th17 cell accumulation and promoted Treg cell gather in the brain, thus protecting mice from experimental autoimmune encephalomyelitis (EAE). These results suggest that Sora may be a potential treatment for autoimmune diseases.