%0 Journal Article
%T CD4+ T-cell Subsets and Cytokine Signature in Pemphigus Foliaceus Clinical Stratification beyond the th1/Th2 Paradigm.
%A Raouia F
%A Mariem BJ
%A Nesrine E
%A Meriam M
%A Mohany M
%A Emna B
%A Sellami K
%A Sawsan F
%A Milošević M
%A Hamida T
%A Hatem M
%A Olfa A
%J Curr Mol Med
%V 0
%N 0
%D 2024 Jun 24
%M 38918985
%F 2.616
%R 10.2174/0115665240305096240611064617
%X <B>BACKGROUND: </B>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.<BR><B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.