T-cell receptor-mediated characteristic signaling pathway of peripheral blood T cells in dermatomyositis and polymyositis

Abstract

The characteristics of T cell expression in peripheral blood have been previously described in dermatomyositis (DM) and polymyositis (PM); however, their intracellular signaling profiles remain unknown. The purpose of this study was to investigate the T-cell receptor (TCR)-mediated intracellular signaling in peripheral blood T cells in DM and PM. Peripheral blood T cells from 86 patients with DM (n = 57) and PM (n = 29) were used for experimental investigations. T-cell subtypes and TCR-induced phosphorylated zeta-chain-associated protein kinase 70 (pZAP70) were analyzed by flow cytometry. Signal transducer and activator of transcription (STAT) and some inhibitory factors in T cells with TCR stimulation were also investigated by quantitative real-time polymerase chain reaction. T cell counts were significantly lower in DM than in PM. In addition, STAT, forkhead box transcription factor (FoxP3), and pZAP70 expression in CD4⁺ T cells was suppressed in DM, whereas STAT and pZAP70 expression in CD8⁺ T cells was induced in PM. Especially in DM, a positive correlation between CD4⁺ T cell counts and STAT expression was detected. In addition, low CD4⁺ T cell counts as well as reduced STAT expression were prominent in patients with interstitial lung disease. STAT and pZAP70 expression significantly improved after clinical remission in both DM and PM, although expression of FoxP3 remained suppressed. Besides, upregulation of suppressor of cytokine signaling-3 (SOCS3) and downregulation of interleukin 6 signal transducer (IL6ST) in CD4⁺ T cells were observed in both DM and PM; however, no significant improvements were detected after clinical remission. The results of the present study suggested that TCR-mediated signaling may be a key pathway to determine the different characteristics of peripheral blood T cells between DM and PM. In addition, upregulation of SOCS3 and downregulation of IL6ST and FoxP3 in CD4⁺ T cells may cause an imbalance in intracellular signaling, especially in DM, suggesting that further studies are required to identify how the impaired signaling contributes to the development of the disease.

Keywords:

• Dermatomyositis
• polymyositis
• peripheral blood T cell
• T-cell receptor
• signal transducer and activator of transcription

Acknowledgements

We wish to thank all the members of the Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine and Dr. Shu-ichi Ikeda for the efforts of medical care, and Dr. C. Weyand for the technical advice. This study was supported by a grant from the Ministry of Health, Labour and Welfare of Japan.

Disclosure statement

The authors declare that they have no financial or personal conflicts of interest.