Abstract
Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) play a pivotal role in the preservation of self-tolerance, and Treg dysfunction has been implicated in many autoimmune diseases. Whether and how Tregs participate in the pathogenesis of ankylosing spondylitis (AS) has not been fully elucidated. Here, we investigated Treg function and found that Tregs in peripheral blood (PB) from patients with active AS had lower FoxP3 mean fluorescence intensity (MFI) than those from healthy controls and could not fully suppress naïve T cell (Tn) proliferation. We also studied the mechanisms underlying PB Treg dysfunction in this context and found that PB Tregs failed to effectively utilize IL-2 and had relatively little STAT5 phosphorylation in active AS. Moreover, PB Tregs from patients with active AS exhibited greater CpG island methylation in the CNS2 region of the FOXP3 gene. Therefore, our findings indicate that functional defects in Tregs are present in AS. Abnormal IL-2 signalling and aberrant CNS2 epigenetic control induced functional defects in PB Tregs and represents a potential new mechanism for AS pathogenesis. These findings may aid the design of new treatment approaches for AS.
Highlights
Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) play a pivotal role in the preservation of self-tolerance, and Treg dysfunction has been implicated in many autoimmune diseases
We found no significant differences in any of these values between peripheral blood (PB) samples collected from patients with active Ankylosing spondylitis (AS) and those collected from healthy controls (Fig. 1a)
We focused on PB Treg function and found that PB Tregs are functionally impaired in active AS
Summary
Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) play a pivotal role in the preservation of self-tolerance, and Treg dysfunction has been implicated in many autoimmune diseases. Whether and how peripheral blood (PB) Tregs control AS severity are questions that remain unresolved Both the number and function of PB Tregs are crucial for the suppression of inflammatory and autoimmune pathology, and disruptions in both factors have been implicated in the pathogenesis of many inflammatory and autoimmune diseases[9], including type 1 diabetes (T1D)[10] and multiple sclerosis (MS)[11]. No studies have investigated the roles of CNS2 methylation and PB Treg function in autoimmune disorders such as AS. How these factors affect patients with AS warrants further investigation. To investigate the issues described above, the present study was designed to measure the frequencies and examine the functions of various PB CD4+ T cell subsets, especially the suppressive function of PB Tregs, in AS www.nature.com/scientificreports/
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