Decreased expression of Runx1 and lowered proportion of Foxp3⁺ CD25⁺ CD4⁺ regulatory T cells in systemic sclerosis

Abstract

Objectives. To investigate the role of Foxp3⁺ CD25⁺ CD4⁺ regulatory T cells (Treg) and their transcription factor, Runt-related transcription factor 1 (Runx1), in the pathogenesis and development of systemic sclerosis (SSc).

Methods. We collected 23 blood samples from patients with SSc including 19 females and 4 males, 11 early-stage cases within 3 years from onset and 12 late-stage cases and 22 samples from age-matched healthy subjects (HS). Total CD4⁺ T cells were assessed for the expression of Treg-related markers, CD25 and CD127, on their surface and intracellular Foxp3 using flow cytometry. Relative expression of Runx1 mRNA in magnetically purified Treg was analyzed using real-time PCR.

Results. Proportion of Foxp3⁺ cells in total CD4⁺ T cells was decreased in patients with either early- or late-stage SSc compared with that in HS, and Runx1 mRNA expression in purified Treg was lower in patients with SSc than in HS. Runx1 mRNA expression level was related to the frequency of Treg in SSc.

Conclusions. This is the first report on Runx1 expression in Treg of a human autoimmune disease. Low expression of Runx1 along with reduced proportion of Treg in CD4⁺ T cells may be associated with development of SSc even in early disease.

Keywords:

• Foxp3
• Runx1
• Regulatory T cell
• Systemic sclerosis

Acknowledgement

This work was supported by KAKENHI (grant-in-aid for Young Scientists (B): 21790931) granted from The Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. We thank M. Aoto, H. Miidera, Y. Nakagawa, H. Nakagawa and T. Terada for their technical assistance.

Conflict of interest

None.