{"title":"丘疹性天疱疮临床分层中的 CD4+ T 细胞亚群和细胞因子特征超越了 th1/Th2 范式。","authors":"Fakhfakh Raouia, Ben Jmaa Mariem, Elloumi Nesrine, Mseddi Meriam, Mohamed Mohany, Bahloul Emna, Khadija Sellami, Feki Sawsan, Marija Milošević, Turki Hamida, Masmoudi Hatem, Abida Olfa","doi":"10.2174/0115665240305096240611064617","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>T helper interplay and cytokines monitoring in auto-immune skin disorders such as Pemphigus Foliaceus [PF] may play a central role in predicting the clinical stratification of the pathology.</p><p><strong>Objectives: </strong>In order to assess the CD4+ T cell imbalance, [i] this study aims to assess the related immune cells [Th1, Th2, Th17, and Treg cells] as well as the related cytokines [IL-1β, IFNγ, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL- 22, TNF-β, and TNFα] in peripheral blood, and [ii] their respective transcription factors in the lesioned skin of PF endemic patients during the clinical course.</p><p><strong>Methods: </strong>Peripheral blood of 22 PF patients was analyzed by flow cytometry to assess the functional associations of Th cell subpopulations and their characteristic cytokines by multiplex bead assay of 14-plex cytokines. Skin mRNA expression of their associated transcription factors was analyzed using the TaqMan detection system.</p><p><strong>Results: </strong>Our findings revealed that the CD4+ T cell subtypes in PF patients compared to Healthy Controls [HC] were characterized by [i] a similar Th1/Th2 ratio and increased Th17/Treg ratio and [ii] significantly higher plasma levels of Th-17 specific cytokines; IL- 6, IL-8, IL-17A. Higher percentages in Th17 and Treg subtypes and a significant increase in plasma IL-17F levels were maintained in relapsing PF patients, arguing the pivotal role of Th17 cells in PF pathogenesis. Furthermore, our findings pointed out the major contribution of the pro-inflammatory cytokine IL-6. Indeed, in addition to being involved in the initial stages of disease development, IL-6 seems to also be involved in the maintenance of the pathophysiological process, probably through its effect on Th17 differentiation. The skin-relative mRNA expression levels of FOXP3 and TBET were significantly higher in relapsing PF patients compared to de novo PF patients.</p><p><strong>Conclusion: </strong>Our results highlight the central role played by Th17 lymphocytes and their related pro-inflammatory cytokines during the clinical course of the disease, reversing the Th1/Th2 dichotomy in PF.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CD4+ T-cell Subsets and Cytokine Signature in Pemphigus Foliaceus Clinical Stratification beyond the th1/Th2 Paradigm.\",\"authors\":\"Fakhfakh Raouia, Ben Jmaa Mariem, Elloumi Nesrine, Mseddi Meriam, Mohamed Mohany, Bahloul Emna, Khadija Sellami, Feki Sawsan, Marija Milošević, Turki Hamida, Masmoudi Hatem, Abida Olfa\",\"doi\":\"10.2174/0115665240305096240611064617\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>T helper interplay and cytokines monitoring in auto-immune skin disorders such as Pemphigus Foliaceus [PF] may play a central role in predicting the clinical stratification of the pathology.</p><p><strong>Objectives: </strong>In order to assess the CD4+ T cell imbalance, [i] this study aims to assess the related immune cells [Th1, Th2, Th17, and Treg cells] as well as the related cytokines [IL-1β, IFNγ, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL- 22, TNF-β, and TNFα] in peripheral blood, and [ii] their respective transcription factors in the lesioned skin of PF endemic patients during the clinical course.</p><p><strong>Methods: </strong>Peripheral blood of 22 PF patients was analyzed by flow cytometry to assess the functional associations of Th cell subpopulations and their characteristic cytokines by multiplex bead assay of 14-plex cytokines. Skin mRNA expression of their associated transcription factors was analyzed using the TaqMan detection system.</p><p><strong>Results: </strong>Our findings revealed that the CD4+ T cell subtypes in PF patients compared to Healthy Controls [HC] were characterized by [i] a similar Th1/Th2 ratio and increased Th17/Treg ratio and [ii] significantly higher plasma levels of Th-17 specific cytokines; IL- 6, IL-8, IL-17A. Higher percentages in Th17 and Treg subtypes and a significant increase in plasma IL-17F levels were maintained in relapsing PF patients, arguing the pivotal role of Th17 cells in PF pathogenesis. Furthermore, our findings pointed out the major contribution of the pro-inflammatory cytokine IL-6. Indeed, in addition to being involved in the initial stages of disease development, IL-6 seems to also be involved in the maintenance of the pathophysiological process, probably through its effect on Th17 differentiation. The skin-relative mRNA expression levels of FOXP3 and TBET were significantly higher in relapsing PF patients compared to de novo PF patients.</p><p><strong>Conclusion: </strong>Our results highlight the central role played by Th17 lymphocytes and their related pro-inflammatory cytokines during the clinical course of the disease, reversing the Th1/Th2 dichotomy in PF.</p>\",\"PeriodicalId\":10873,\"journal\":{\"name\":\"Current molecular medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-06-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current molecular medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0115665240305096240611064617\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115665240305096240611064617","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
CD4+ T-cell Subsets and Cytokine Signature in Pemphigus Foliaceus Clinical Stratification beyond the th1/Th2 Paradigm.
Background: T helper interplay and cytokines monitoring in auto-immune skin disorders such as Pemphigus Foliaceus [PF] may play a central role in predicting the clinical stratification of the pathology.
Objectives: In order to assess the CD4+ T cell imbalance, [i] this study aims to assess the related immune cells [Th1, Th2, Th17, and Treg cells] as well as the related cytokines [IL-1β, IFNγ, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL- 22, TNF-β, and TNFα] in peripheral blood, and [ii] their respective transcription factors in the lesioned skin of PF endemic patients during the clinical course.
Methods: Peripheral blood of 22 PF patients was analyzed by flow cytometry to assess the functional associations of Th cell subpopulations and their characteristic cytokines by multiplex bead assay of 14-plex cytokines. Skin mRNA expression of their associated transcription factors was analyzed using the TaqMan detection system.
Results: Our findings revealed that the CD4+ T cell subtypes in PF patients compared to Healthy Controls [HC] were characterized by [i] a similar Th1/Th2 ratio and increased Th17/Treg ratio and [ii] significantly higher plasma levels of Th-17 specific cytokines; IL- 6, IL-8, IL-17A. Higher percentages in Th17 and Treg subtypes and a significant increase in plasma IL-17F levels were maintained in relapsing PF patients, arguing the pivotal role of Th17 cells in PF pathogenesis. Furthermore, our findings pointed out the major contribution of the pro-inflammatory cytokine IL-6. Indeed, in addition to being involved in the initial stages of disease development, IL-6 seems to also be involved in the maintenance of the pathophysiological process, probably through its effect on Th17 differentiation. The skin-relative mRNA expression levels of FOXP3 and TBET were significantly higher in relapsing PF patients compared to de novo PF patients.
Conclusion: Our results highlight the central role played by Th17 lymphocytes and their related pro-inflammatory cytokines during the clinical course of the disease, reversing the Th1/Th2 dichotomy in PF.
期刊介绍：
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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