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- W4313373578 abstract "Abstract Pemphigus vulgaris (PV) is an autoimmune bullous disease mediated by autoantibodies against desmoglein (DSG) 3 which is the adhesive molecule in the desmosomes. DSG3-specific CD4+ helper T cells have been demonstrated to be involved in autoantibody production and pathogenesis in mouse models and human patients. However, it remains unknown if T follicular helper (Tfh) cells expressing ICOS play a role in the pathogenesis of PV although ICOS+ Tfh cells have a critical role in various autoimmune diseases. The aim of this study was to analyze the immunological characteristics and pathogenic roles of ICOS+ Tfh cells using PV mouse model and peripheral blood mononuclear cells (PBMCs) from pemphigus patients. In addition, we tried to investigate the therapeutic effect of ICOS-ICOSL blockade in PV mice. We immunized the DSG3−/− mice by grafting skin of wild-type mice, then we adoptively transferred CD4+ T and B cells from the DSG3-primed DSG3−/− mice to RAG1−/− mice. We found that ICOS+ Tfh cells were associated with B cell development in the mouse model. By using an MHC class II tetramer, we showed that DSG3-specific ICOS+ Tfh cells were increased and significantly related to the level of anti-DSG3 antibody. In PBMCs from the patients with pemphigus vulgaris, the frequency of ICOS+CXCR5+PD-1+ memory CD4+ T cells was positively correlated with DSG3 autoantibody levels. Furthermore, the administration of anti-ICOS blocking antibody to PV mice in vivo decreased the production of anti-DSG3 antibody and prevented disease activation. Therefore, ICOS+CXCR5+PD-1+ T helper cells are associated with the disease progression and can be a therapeutic target for PV." @default.
- W4313373578 created "2023-01-06" @default.
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- W4313373578 date "2020-05-01" @default.
- W4313373578 modified "2023-09-22" @default.
- W4313373578 title "Role of ICOS expressing CXCR5+PD-1+ T helper cells in pemphigus vulgaris" @default.
- W4313373578 doi "https://doi.org/10.4049/jimmunol.204.supp.224.22" @default.
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