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 <i>IL23R</i>, <i>RORγt</i>, <i>IL17A</i>, <i>IL17F</i>, <i>IL17AR</i>, <i>TNFa</i>, and <i>STAT3</i> genes were genotyped. mRNA expression of <i>IL23R</i> and <i>RORγt</i> was evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations between <i>IL23R</i>>rs11209026, <i>IL17A</i>>rs3748067, <i>IL17F</i>>rs763780, and <i>TNFa</i>>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<i>γ</i>t and IL23R in PBMCs of patients. However, no significant increase of ROR<i>γ</i>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.