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Skewed X chromosomal inactivation impacts T regulatory cell function in systemic sclerosis
Jasper C A Broen1, Ingrid L M Wolvers-Tettero, Lenny Geurts-van Bon
1Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Annals of the Rheumatic Diseases
|August 12, 2010
Summary
Skewed X chromosomal inactivation (XCI) is linked to systemic sclerosis (SSc) susceptibility. This skewing impacts forkhead box P3 (Foxp3) expression and T regulatory cell (Treg) function in SSc patients.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- Systemic sclerosis (SSc) is an autoimmune disease with complex etiology.
- X chromosomal inactivation (XCI) patterns can vary and may influence immune cell function.
- T regulatory cells (Tregs) play a crucial role in immune tolerance.
Purpose of the Study:
- To investigate the role of XCI in SSc pathogenesis.
- To examine the impact of XCI on forkhead box P3 (Foxp3) expression in Tregs from SSc patients.
Main Methods:
- Assessed XCI patterns using the Human Androgen Receptor Assay in 217 women with SSc and 107 controls.
- Analyzed DNA from various immune cell subsets.
- Measured intracellular Foxp3 expression in CD4+ CD25+ cells via flow cytometry.
Main Results:
- Significantly higher frequency of skewed XCI observed in SSc patients compared to controls.
- Skewed XCI was associated with lower Foxp3 expression and reduced suppressive capacity in Tregs.
- No difference in XCI skewing was found between immune cell subsets.
Conclusions:
- Skewed XCI is implicated in SSc susceptibility.
- XCI skewing influences Foxp3 expression and Treg suppressive function in SSc.
- The findings highlight a potential mechanism linking XCI to SSc pathogenesis.
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