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Sorafenib inhibits multiple sclerosis by regulating T cell differentiation.
Hanliang Wang1, Shuowang Wang2, Jin Wang3
1Department of Breast Surgery, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang 310006, China; Department of Medical Oncology, Cancer Center of Zhejiang University, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, Zhejiang 310020, China.
Cellular Signalling
|May 19, 2025
Summary
Sorafenib, an FDA-approved tumor drug, effectively suppresses pro-inflammatory T helper 1 and T helper 17 cells while promoting anti-inflammatory regulatory T cells, offering potential for autoimmune disease treatment.
Area of Science:
- Immunology
- Pharmacology
- Neuroscience
Background:
- Multiple sclerosis (MS) involves aberrant T cell responses and loss of immune tolerance, leading to chronic inflammation and tissue damage.
- CD4+ T helper (Th) cells differentiate into distinct subtypes (Th1, Th2, Th17, Treg) influencing immune responses.
Purpose of the Study:
- To investigate the effect of sorafenib (Sora), a tyrosine kinase inhibitor, on T cell differentiation in the context of autoimmune diseases.
- To elucidate the signaling pathways targeted by sorafenib in modulating T cell responses.
Main Methods:
- In vitro analysis of T cell differentiation under sorafenib treatment.
- In vivo studies using experimental autoimmune encephalomyelitis (EAE) mouse model.
- Assessment of STAT4 and TGF-β1 signaling pathways.
Main Results:
- Sorafenib suppressed the differentiation of pro-inflammatory Th1 and Th17 cells.
- Sorafenib promoted the polarization of anti-inflammatory Treg cells.
- Sorafenib inhibited Th1 and Th17 cell accumulation in the brain and enhanced Treg cell presence in EAE mice.
- Sorafenib acted via STAT4 and TGF-β1 signaling pathways to suppress Th1 and Th17 differentiation, respectively.
Conclusions:
- Sorafenib demonstrates immunomodulatory effects by rebalancing T cell populations.
- Sorafenib exhibits therapeutic potential for experimental autoimmune encephalomyelitis and possibly other autoimmune diseases.
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