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Decreased expression of Runx1 and lowered proportion of Foxp3⁺ CD25⁺ CD4⁺ regulatory T cells in systemic sclerosis
Hiroshi Kataoka1, Shinsuke Yasuda, Shinji Fukaya
1Department of Medicine II, Hokkaido University Graduate School of Medicine , Sapporo , Japan.
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.
Insights
Regulatory T cells (Treg) and their transcription factor, Runt-related transcription factor 1 (Runx1), are crucial in systemic sclerosis (SSc). Lower Treg proportions and Runx1 expression in SSc patients suggest a role in disease development.
Area of Science:
- Immunology
- Autoimmune Diseases
- Molecular Biology
Background:
- Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis.
- Regulatory T cells (Treg) play a critical role in maintaining immune tolerance.
- The transcription factor Runt-related transcription factor 1 (Runx1) is involved in T cell development and function.
Purpose of the Study:
- 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).
Main Methods:
- Collected blood samples from 23 SSc patients (19 female, 4 male; 11 early-stage, 12 late-stage) and 22 age-matched healthy subjects (HS).
- Assessed Treg markers (CD25, CD127, intracellular Foxp3) on CD4(+) T cells using flow cytometry.
- Analyzed Runx1 mRNA expression in purified Treg via real-time PCR.
Main Results:
- The proportion of Foxp3(+) Treg cells within total CD4(+) T cells was significantly decreased in SSc patients (early and late-stage) compared to HS.
- Runx1 mRNA expression in purified Treg was significantly lower in SSc patients than in HS.
- A positive correlation was observed between Runx1 mRNA expression level and the frequency of Treg in SSc patients.
Conclusions:
- This study is the first to report Runx1 expression in Treg from patients with a human autoimmune disease.
- Reduced proportion of Treg cells and decreased Runx1 expression in CD4(+) T cells may be associated with the development of SSc, even in the early stages.
- These findings highlight a potential role for Treg dysfunction and altered Runx1 expression in SSc pathogenesis.
