TLR4-MyD88-NF-κB signaling imbalances Th17 and Treg cells in thymoma with myasthenia gravis

R.-Y. Zhang, X.-S. Zhang, C. Lu, Z.-R. Wang, Y. Shi, Y.-G. Wang, P. Zhang, Y. Chen

Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Heping District, Tianjin, China. yuanchen@tmu.edu.cn

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• Immunology

OBJECTIVE: Thymus is an immune organ in which pathological changes may cause autoimmune diseases, including myasthenia gravis (MG). Recent studies have focused on Toll-like receptor 4 (TLR4) signaling as the cause of such changes. In our previous study, an imbalance of T helper 17 (Th17) cells and T regulatory (Treg) cells was found in MG thymoma. These results suggest the involvement of TLR4 in the pathogenesis of thymoma MG via an alteration of the Th17/Treg balance. Here, we aimed to assess whether the TLR4-MyD88-NF-κB pathway is upregulated in MG thymoma and its relationship with Th17/Treg cells.

PATIENTS AND METHODS: We collect thymoma samples from 54 patients with or without MG, detecting the expression level of TLR4, MyD88, and NF-κB in thymoma tissues. Next, we established an in vitro experiment of coculturing thymoma cells with CD4+ T cells and detected the differentiation of Th17 cells and Treg cells and their marker protein, retinoid-related orphan receptor gamma t (RORγt) and forkhead transcription factor 3 (Foxp3).

RESULTS: We found TLR4, MyD88, and NF-κB expressed more in MG thymoma compared with simple thymoma. After the transwell coculturing, we observed an imbalance of Th17/Treg cells after TLR4 stimulation.

CONCLUSIONS: TLR4 is stimulated in thymoma, causing an increase of Th17 cells and a decrease of Treg cells, namely an imbalance of Th17/Treg cells, resulting in MG.

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