title: Functional defects in CD4+CD25highFoxP3+regulatory cells in ankylosing spondylitis.
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.
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.|Department of Cell Biology, Fourth Military Medical University, China.|National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.|Department of Cell Biology, Fourth Military Medical University, China.|National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.|National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.|National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
authors.forename: Fengfan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.|National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.|National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Cell Biology, Fourth Military Medical University, China.|National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.|National Translational Science Center for Molecular Medicine, Xi'an 710032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D008297:Male; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D050799:STAT5 Transcription Factor