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A potential reciprocal emergence of regulatory T cells in oral lichen planus and pemphigus vulgaris: A meta-analysis.

ABSTRACT: Oral lichen planus (OLP) and pemphigus vulgaris (PV) are 2 common inflammatory mucocutaneous diseases of immune-based etiology. Evidence indicates regulatory T (Treg) cells maybe play a role in the pathogenesis of OLP and PV, which are caused by aberrant immune responses. In this report, 7 eligible case-control studies containing 517 OLP patients and 261 healthy controls (HC) were identified. The level of Tregs was significantly higher in OLP patients than HC (mean difference: 1.79; 95%CI: 0.99, 2.60). On the other hand, 7 eligible case-control studies containing 169 PV patients and 121 HC were identified. Conversely, the level of Tregs was significantly lower in PV patients than HC (mean difference: -2.49; 95%CI: -3.90, -1.08). Collectively, this analysis for the first time reported reciprocal emergence of Tregs in OLP and PV using meta-analysis, and provided an interesting insight into a previously undescribed the linkage of the 2 mucocutaneous diseases.

SUBMITTER: Liu W

PROVIDER: S-EPMC9831822 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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A potential reciprocal emergence of regulatory T cells in oral lichen planus and pemphigus vulgaris: A meta-analysis.

Liu Wei W Zhang Qianqian Q Bao Zhexuan Z Shen Xuemin X

Journal of dental sciences 20220730 1

Oral lichen planus (OLP) and pemphigus vulgaris (PV) are 2 common inflammatory mucocutaneous diseases of immune-based etiology. Evidence indicates regulatory T (Treg) cells maybe play a role in the pathogenesis of OLP and PV, which are caused by aberrant immune responses. In this report, 7 eligible case-control studies containing 517 OLP patients and 261 healthy controls (HC) were identified. The level of Tregs was significantly higher in OLP patients than HC (mean difference: 1.79; 95%CI: 0.99, ...[more]

PMID: 36643241

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Project description:IntroductionWe here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype.MethodsParaffin-embedded skin biopsies from well-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ϵ, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3.ResultsIn LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes.DiscussionOur findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin.

Project description:BackgroundOral lichen planus (OLP) is a chronic autoimmune oral mucosal disease that seriously affects the life quality of the patients. But till now, the exact etiology and pathogenesis of OLP remain unclear. Our study is aimed at finding the key molecules and pathways involved in the pathogenesis mechanisms of OLP, providing more effective therapeutic strategies for OLP.MethodsData from GSE52130 were downloaded from GEO datasets for analysis. Then, we carried out enrichment analysis of the differentially expressed genes (DEGs) using Gene Ontology (GO) and KEGG pathway analyses. Next, the CIBERSORT algorithm was used to assess immune cell infiltration in OLP patients. Furthermore, we also constructed a protein-protein interaction network using STRING and Cytoscape and simultaneously sought potential transcription factors plug-in including MCODE CytoHubba and iRegulon. In addition, ROC analysis was employed to assess the diagnostic performance of these hub genes. Lastly, we identified 6 promising novel drugs to treat OLP through Connectivity Map.ResultsWe illustrated that 255 DEGs were mainly enriched in the focal adhesion pathway and metabolism pathways. Besides, Cibersort analysis showed that M1 macrophages, T follicular helper cells, and T regulatory cells are more infiltrated in OLP samples. In addition, ROC analysis demonstrated that these hub genes owned higher diagnostic value in OLP, in which SPRR1B had the highest diagnostic value. And we also predicted that SOX7 was the most relevant transcription factor of those hub genes. Lastly, through the CMap database, we identified 6 small molecules as possible treatment drugs of OLP.ConclusionOur research identified that SPRR1B could be used as potential biomarkers for the early diagnosis of OLP. In addition, as a chronic autoimmune oral mucosal disease, OLP has different infiltration types of immune cells. Furthermore, 6 small molecules were proposed as promising novel treatment drugs for OLP patients. Therefore, our research may provide new impetus for the development of effective OLP biological treatment options.

Dataset Information

A potential reciprocal emergence of regulatory T cells in oral lichen planus and pemphigus vulgaris: A meta-analysis.

Publications

A potential reciprocal emergence of regulatory T cells in oral lichen planus and pemphigus vulgaris: A meta-analysis.

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