Frequently Increased but Functionally Impaired CD4+CD25+ Regulatory T Cells in Patients with Oral Lichen Planus.
Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucosal disease, and CD4(+)CD25(+) regulatory T cells (Tregs) are considered involved in the pathogenesis of OLP. In this study, to investigate whether there are intrinsic factors that might cause functional changes in Tregs in this disease, we evaluated the frequency of Tregs in peripheral blood and oral lesions and the expression levels of function-related transcription factors, forkhead/winged-helix transcription factor box P3 (FOXP3), transforming growth factor β (TGF-β), interleukin 10 (IL-10), and TGF-β receptors (TβRI and TβRII) mRNAs in Tregs of patients with oral lichen planus (OLP). We also investigated the frequency of pro-inflammatory cytokines (IFN-γ and IL-17A) producing Foxp3(+) regulatory cells. Increased proportions of Tregs were found in OLP patients. The expression of FOXP3 on mRNA and protein level was elevated in the Tregs of OLP. The expression of TGF-β was lower both on the mRNA and serum level, whereas the expression of IL-10 showed no significant difference between the OLP patients and normal controls. The percentages of CD4(+)FOXP3(+)IL-17(+) T cells were significantly higher than that of normal controls, whereas the percentages of CD4(+)FOXP3(+)IFN-γ(+) T cells did not differ significantly. Furthermore, impaired suppressive function of CD4(+)CD25(+) T cells was demonstrated in OLP patients by in vitro proliferation assay. These data indicate that Tregs in OLP are frequently expanded but functionally deficient. This could explain, at least in part, why the increased Tregs in OLP fail to control the pathogenesis and development of this autoimmune disease.
Shanghai Key Laboratory of Stomatology, Department of Oral Mucosal Diseases, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Leilei
L
Zhou
Shanghai Key Laboratory of Stomatology, Department of Oral Mucosal Diseases, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Tianyi
T
Cao
Shanghai Key Laboratory of Stomatology, Department of Oral Mucosal Diseases, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Yufeng
Y
Wang
Shanghai Key Laboratory of Stomatology, Department of Oral Mucosal Diseases, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Hui
H
Yao
Shanghai Key Laboratory of Stomatology, Department of Oral Mucosal Diseases, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
Guanhuan
G
Du
Department of Immunology, Institutes of Medical Sciences, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Guangjie
G
Chen
Department of Immunology, Institutes of Medical Sciences, Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Xiaoyin
X
Niu
Shanghai Key Laboratory of Stomatology, Department of Oral Mucosal Diseases, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China. tanggy@shsmu.edu.cn.
Guoyao
G
Tang
D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics; D020381:Interleukin-17 / Q000032:analysis / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit; D017676:Lichen Planus, Oral / Q000097:blood* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C573415:IFNG protein, human; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D007371:Interferon-gamma
FOXP3; IL-10; IL-17A; TGF-β; oral lichen planus; regulatory T cells