2018•Mediators of InflammationOpen access

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

Mariem Ben Jmaa, Olfa Abida, Raouia Fakhfakh, emna bahloul, K. Sellami, Lilia Gaddour, Nésrine Elloumi, Mourad Ben Ayed, Abderrahmen Masmoudi, Morched Dhouib, Mohamed Hedi Abdelmoula, Nadia Mahfoudh, H. Makni, Hamida Turki, Hatem Masmoudi

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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 inIL23R,RORγt,IL17A,IL17F,IL17AR,TNFa, andSTAT3genes were genotyped. mRNA expression ofIL23RandRORγtwas evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations betweenIL23R>rs11209026,IL17A>rs3748067,IL17F>rs763780, andTNFa>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 RORγt and IL23R in PBMCs of patients. However, no significant increase of RORγt 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.

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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 inIL23R,RORγt,IL17A,IL17F,IL17AR,TNFa, andSTAT3genes were genotyped. mRNA expression ofIL23RandRORγtwas evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations betweenIL23R>rs11209026,IL17A>rs3748067,IL17F>rs763780, andTNFa>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 RORγt and IL23R in PBMCs of patients. However, no significant increase of RORγt 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.

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Available 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 inIL23R,RORγt,IL17A,IL17F,IL17AR,TNFa, andSTAT3genes were genotyped. mRNA expression ofIL23RandRORγtwas evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations betweenIL23R>rs11209026,IL17A>rs3748067,IL17F>rs763780, andTNFa>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 RORγt and IL23R in PBMCs of patients. However, no significant increase of RORγt 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.

Key concepts: Pemphigus foliaceus, Interleukin 23, Pathogenesis, RAR-related orphan receptor gamma, Interleukin 17, Immunology, Biology, Flow cytometry

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