Involvement of the IL23/Th17 Pathway in the Pathogenesis of Tunisian Pemphigus Foliaceus

Abstract

Pemphigus foliaceus (PF) is a rare autoimmune skin disease caused by anti-Dsg1 pathogenic autoantibodies. It is considered as a Th2-mediated disease. Likewise, Th17 cells were recently described in the pathogenesis of the disease but their role is still unclear. We aimed to unravel the eventual implication of the IL23/Th17 pathway in the development of PF. A case-control study was conducted on 115 PF patients and 201 healthy controls using PCR-RFLP and AS-PCR methods. SNPs in IL23R , RORγt , IL17A , IL17F , IL17AR , TNFa , and STAT3 genes were genotyped. mRNA expression of IL23R and RORγt was evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations between IL23R >rs11209026, IL17A >rs3748067, IL17F >rs763780, and TNFa >rs1800629 and the susceptibility to PF were reported. Moreover, we revealed a significant increased frequency of circulating CD4 + IL17 + cells as well as higher mRNA levels of ROR γ t and IL23R in PBMCs of patients. However, no significant increase of ROR γ t and IL23R mRNA expression was observed in lesional skin biopsies. In spite of the little size of specimens, our results provide converging arguments for the contribution of the IL23/Th17 pathway in the pathogenesis of PF.