Author(s): Fakhfakh Raouia, Ben Jmaa Mariem, Elloumi Nesrine, Mseddi Meriam, Mohamed Mohany*, Bahloul Emna, Khadija Sellami, Feki Sawsan, Marija Milošević, Turki Hamida, Masmoudi Hatem and Abida Olfa*
Page: [485 - 495] Pages: 11
* (Excluding Mailing and Handling)
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.
Keywords: Pemphigus, Th classical phenotype, cytokines, prediction, clinical stratification, CD4+ T-cell.
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