CD4+ T-cell Subsets and Cytokine Signature in Pemphigus Foliaceus Clinical Stratification beyond the th1/Th2 Paradigm

Author:

Raouia Fakhfakh1,Mariem Ben Jmaa1,Nesrine Elloumi1,Meriam Mseddi2,Mohany Mohamed3,Emna Bahloul4,Sellami Khadija4,Sawsan Feki5,Milošević Marija6,Hamida Turki4,Hatem Masmoudi15,Olfa Abida1

Affiliation:

1. “Autoimmunity, Cancer and Immunogenetics” research laboratory [LR18SP12], Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia

2. Laboratory of Research 'Molecular Basis of Human Diseases', LR19ES13, Faculty of Medicine, University of Sfax, Sfax, Tunisia

3. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia

4. Dermatology Department, Hedi Chaker Hospital, University of Sfax, Sfax, Tunisia

5. Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia

6. Department of Biology and Ecology, Faculty of Science, University of Kragujevac, 34000 Kragujevac, Serbia

Abstract

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.

Publisher

Bentham Science Publishers Ltd.

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