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学科主题: 临床医学
题名:
Elevated Levels of CD4(+)CD25(+)FoxP3(+) T Cells in Systemic Sclerosis Patients Contribute to the Secretion of IL-17 and Immunosuppression Dysfunction
作者: Liu, Xinjuan1,2; Gao, Na1,2; Li, Mengtao1,2; Xu, Dong1,2; Hou, Yong1,2; Wang, Qian1,2; Zhang, Guohua1,2; Sun, Qiuning2,3; Zhang, Henghui4; Zeng, Xiaofeng1,2
刊名: PLOS ONE
发表日期: 2013-06-11
DOI: 10.1371/journal.pone.0064531
卷: 8, 期:6
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: TGF-BETA ; INCREASED FREQUENCY ; REGULATORY CELLS ; CTLA-4 GENE ; EXPRESSION ; TH17 ; ASSOCIATION ; DISEASE ; FOXP3 ; ACTIVATION
英文摘要:

Objective: Immune imbalance between regulatory T (Treg) and Th17 cells is a characteristic of systemic sclerosis (SSc). The functional heterogeneity among Treg can be elucidated by separating Treg into different subsets based on the expression of FoxP3 and CD45RA. The aim of this study was to investigate the role of Treg subsets in the immune imbalance in naive SSc.

Methods: Peripheral blood mononuclear cells (PBMCs) of 31 SSc patients and 33 healthy controls were analyzed for the expression of CD4, CD25, CD45RA, CTLA-4, FoxP3, and IL-17 using flow cytometry. Treg immunesuppression capacity was measured in co-culture experiments. The expression of FoxP3, CTLA-4, IL-17A, and RORC mRNA was measured by real-time PCR.

Results: The frequency of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly elevated in patients with SSc (3.62 +/- 1.14 vs 1.97 +/- 0.75, p<0.001) with diminished immunosuppression capacity. In SSc, the proportion of FoxP3(high)CD45RA(-) activated Treg cells (aTreg) was decreased, the proportion of FoxP3(low)CD45RA(-) T cells was increased, and the proportion of FoxP3(low)CD45RA(+) resting Treg cells (rTreg) was decreased. The immune suppression capacity of aTreg and rTreg was diminished, while FoxP3(low)CD45RA(-) T cells exhibited a lack of suppression capacity. The immune dysfunction of aTreg was accompanied by the abnormal expression of CTLA-4. Th17 cell numbers were elevated in SSc, FoxP3(low)CD45RA(-) T cells produced IL-17, confirming their Th17 potential, which was consistent with the elevated levels of FoxP3(+)IL-17(+) cells in SSc.

Conclusion: A decrease in aTreg levels, along with functional deficiency, and an increase in the proportion of FoxP3(low)CD45RA(-) T cells, was the reason for the increase in dysfunctional Treg in SSc patients, potentially causing the immune imbalance between Treg and Th17 cells.

语种: 英语
所属项目编号: 81072485 ; 81001072 ; 81071300 ; 81102268
项目资助者: National Natural Science Foundation of China ; EULAR Scleroderma Trial &amp ; Research group (EUSTAR), Fund of Capital Medical Development and Research
WOS记录号: WOS:000320755400008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62010
Appears in Collections:北京大学第二临床医学院_北京大学肝病研究所_期刊论文

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作者单位: 1.Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Rheumatol, Beijing 100730, Peoples R China
2.Peking Union Med Coll, Beijing 100021, Peoples R China
3.Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Dermatol, Beijing 100730, Peoples R China
4.Peking Univ, Inst Hepatol, Peoples Hosp, Beijing Key Lab Hepatitis C & Immunotherapy Liver, Beijing 100871, Peoples R China

Recommended Citation:
Liu, Xinjuan,Gao, Na,Li, Mengtao,et al. Elevated Levels of CD4(+)CD25(+)FoxP3(+) T Cells in Systemic Sclerosis Patients Contribute to the Secretion of IL-17 and Immunosuppression Dysfunction[J]. PLOS ONE,2013,8(6).
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