Didona, DarioDarioDidonaScarsella, LucaLucaScarsellaHudemann, ChristophChristophHudemannVolkmann, KarolinKarolinVolkmannZimmer, Christine LChristine LZimmerBeckert, BenediktBenediktBeckertTikkanen, RitvaRitvaTikkanenKorff, VeraVeraKorffKühn, KatjaKatjaKühnWienzek-Lischka, SandraSandraWienzek-LischkaBein, GregorGregorBeindi Zenzo, GiovanniGiovannidi ZenzoBöhme, JaquelineJaquelineBöhmeCunha, TomasTomasCunhaSolimani, FarzanFarzanSolimaniPieper, JosquinJosquinPieperJuratli, Hazem AHazem AJuratliGöbel, ManuelManuelGöbelSchmidt, ThomasThomasSchmidtBorradori, LucaLucaBorradoriYazdi, Amir SAmir SYazdiSitaru, CassianCassianSitaruGarn, HolgerHolgerGarnEming, RüdigerRüdigerEmingFleischer, SabineSabineFleischerHertl, MichaelMichaelHertl2024-10-252024-10-252024-02https://boris-portal.unibe.ch/handle/20.500.12422/170034Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies which predominantly target two transmembrane desmosomal cadherins, desmoglein (Dsg)1 and Dsg3. Dsg-specific T cells play a central role in PV pathogenesis as they provide help to autoreactive B cells for autoantibody production. We here characterized Dsg3-specific peripheral T cells in a cohort of 52 PV patients and 41 healthy controls (HC) with regard to cytokine profile and epitope specificity. By ELISpot analysis, type 2 T cells reactive with the Dsg3 ectodomain were significantly increased in PV patients compared to HC. By dextramer analysis, CD4+ T cells specific for an epitope within the extracellular domain of Dsg3, Dsg3(206-220), were found at significantly higher frequencies in PV patients than in HLA-matched HC. T cell recognition of two distinct Dsg3 epitopes, i.e. Dsg3(206-220) and Dsg3(378-392), correlated significantly suggesting a synergistic effect in B cell help. Immunization of HLA-DRB1*04:02-transgenic PV mice with the same set of Dsg3 peptides induced pathogenic Dsg3-specific IgG antibodies which induced loss of keratinocyte adhesion in vitro. Thus, Dsg3 peptide-specific T cells are of particular interest as surrogate marker of disease activity and potential therapeutic targets in PV.enT cells autoimmunity bullous disease cytokines regulatory T cells600 - Technology::610 - Medicine & healtharticle10.48350/1863753771793410.1016/j.jid.2023.07.025