FOXP3+ T regulatory cells in lesions of oral lichen planus correlated with disease activity

Tao, Xiaoan; Xia, Juan; Chen, X. B.; Wang, H.; Dai, Yaohui; Rhodus, Nelson L.; Cheng, Bin

doi:10.1111/j.1601-0825.2009.01608.x

Cited by 56 publications

(51 citation statements)

References 34 publications

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“…cells in OLP than in the NSI group and that they were situated in the superficial connective tissue, subjacent the epithelium corroborating the results of others [16,18,20]. Double IF demonstrated that the FoxP3 ?…”

Section: Discussionsupporting

confidence: 91%

“…cells were CD3 ? T cells, reflecting the findings of Tao (2010) [20]. Tregs are involved in immunoregulation, particularly control of autoimmunity through cell-cell contact-mediated suppression.…”

Section: Discussionmentioning

confidence: 91%

“…Higher numbers of FoxP3 ? Tregs have been found in the local environment of OLP by comparison with controls [16,18,20], suggesting that these cells are involved in the pathogenesis of the disease.…”

Section: Introductionmentioning

confidence: 95%

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Regulation of immune cells in oral lichen planus

et al. 2015

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Oral lichen planus (OLP) is an immunological disease and while it is understood that the T cell subsets, FoxP3(+) Tregs and IL17(+) Th17 cells are involved in immune regulation, little is known about their presence in OLP. The aims of this study were to compare the number of cells expressing FoxP3 or IL-17 in OLP with non-specifically inflamed oral mucosa and to determine which cell types expressed FoxP3 and/or IL-17 and their distribution. Immunohistochemistry was used to investigate the presence of FoxP3(+) or IL-17(+) cells in 12 control cases and 17 cases of OLP. These results were analysed quantitatively and qualitatively. Double-labelling immunofluorescence (IF) was used to determine the type of cell expressing FoxP3/IL-17 and these results were analysed qualitatively. OLP displayed significantly more FoxP3(+) cells (mean 79.3 vs. 20.6 cells/defined area, p < 0.0001) and fewer IL-17(+) cells (mean 1.05 vs. 3.30 cells/defined area, p = 0.0003) than non-specific inflammatory cases. The majority of FoxP3(+) cells were in the sub-epithelial infiltrate, while IL-17(+) cells were deeper in the stromal tissues. IF showed that FoxP3(+) cells co-localised with T cells, while the IL-17(+) cells did not. These results show that the balance between Tregs and IL-17(+) cells is altered in OLP, thus supporting the proposition that disturbance in local immune regulation is important in the pathogenesis of OLP. The observation that the IL-17(+) cells were mast cells has not previously been reported in OLP and again raises questions about the role of mast cells in this condition.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 91%

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Regulation of immune cells in oral lichen planus

et al. 2015

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“…Treg and TAM cells are key components of the tumor microenvironment, but Foxp3 is not expressed in normal oral mucosa [20]. In keeping with that observation, we found that OLP, OLK, and OSCC tissues contained inflammatory regions that were infiltrated to different extents by CD4 + T-cells and CD68 + macrophages and that OSCC tissues contained more CD4 + T-cells and CD68 + macrophages than either OLP or OLK tissue.…”

Section: Discussionsupporting

confidence: 85%

Immunosuppression Induced by Chronic Inflammation and the Progression to Oral Squamous Cell Carcinoma

Sun

Liu

Guan

et al. 2016

Mediators of Inflammation

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Oral squamous cell carcinoma (OSCC) is an aggressive, invasive malignancy of epithelial origin. The progression from premalignant lesions—oral leukoplakia (OLK) and oral lichen planus (OLP)—to OSCC involves complex inflammatory processes that have not been elucidated. We investigated the roles of inflammatory mediators and infiltrating immunocytes in the pathogenic progression of OLK and OLP to OSCC. The occurrence of regulatory T-cells (Tregs) and tumor-associated macrophages (TAMs) and the expression of anti-inflammatory cytokines and proinflammatory cytokines were investigated in OLK, OLP, and OSCC tissues. Immunohistochemical staining of CD4, FOXP3, CD68, TGF-β1, IL-10, IL-4, IFN-γ, and MCP-1 showed that the occurrence of Tregs and TAMs increased in parallel with disease progression in OLK and OSCC. IL-10 gradually increased during the early stages of OLK and in OSCC. Infiltrating IL-4+ macrophages were seen with increasing frequency in OLK tissue during the progression of oral dysplasia. Fewer TGF-β1+ macrophages were seen in OSCC than in OLK and OLP. The expression of IFN-γ decreased gradually with the OLK development and had the lowest expression in OSCC. MCP-1 expression did not change significantly during the development of OSCC. The results suggested that the immunosuppression induced by chronic inflammation promotes tumorigenesis in OSCC, rather than initiating it.

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“…21 Yet in another study, which calculated the IFN-γ/IL-4 ratio in lesional tissue and unstimulated whole saliva, the expression of both cytokines were elevated and the IFN-γ/IL-4 ratio showed no significant difference in OLP patients and healthy controls. These controversies might partly be caused by the difference of patients, research methods or sample sizes, but it also implied that there might be some mechanisms, such as the role of regulatory T cells 22 and new subsets of Th cells, 23 in the etiology of OLP other than Th1/Th2 imbalance.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ and interleukin-4 detected in serum and saliva from patients with oral lichen planus

Liu

Long

et al. 2013

Int J Oral Sci

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Our previous salivary study had demonstrated an apparent T helper 2 (Th2)-predominance in saliva of oral lichen planus (OLP) patients and suggested a potential of salivary interleukin-4 (IL-4) as a biomarker for monitoring disease severity. To further determine the consistency of Th1/Th2 bias of OLP, this study investigated the expression profile of interferon-γ (IFN-γ) and IL-4 in serum and the relationship of the serum levels of these cytokines with their saliva partners. Sixty ethnic Chinese patients with OLP (40 of the erythematous/ulcerative form and 20 of the reticular form) were recruited for this study, with 40 age–sex-matched healthy volunteers as control group. IFN-γ and IL-4 levels in serum and paired saliva samples were screened by enzyme-linked immunosorbent assay. OLP patient showed a low-level IFN-γ but high-level IL-4 expression profile in both serum and saliva, with a lower IFN-γ/IL-4 ratio. Serum IL-4 level in the erythematous/ulcerative group was significantly higher than that in the reticular group. Serum levels of IFN-γ and IL-4 were significantly and positively correlated with their saliva partners. These results provided more evidence for Th2 cytokine-predominant immune imbalance in OLP, as well as the potential of IL-4 as the biomarker for monitoring severity of OLP.

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FOXP3+ T regulatory cells in lesions of oral lichen planus correlated with disease activity

Cited by 56 publications

References 34 publications

Regulation of immune cells in oral lichen planus

Regulation of immune cells in oral lichen planus

Immunosuppression Induced by Chronic Inflammation and the Progression to Oral Squamous Cell Carcinoma

Interferon-γ and interleukin-4 detected in serum and saliva from patients with oral lichen planus

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