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- W4366179664 abstract "Bullous pemphigoid (BP) is an autoimmune blistering disorder induced by autoantibodies against type XVII collagen (COL17). COL17-reactive CD4+ T cells have been shown to play an important role in the pathogenesis of BP. However, the characteristics of pathogenic COL17-reactive CD4+ T cells remain unclear. In this study, we sought to establish COL17-reactive CD4+ T cell clones and elucidate their pathogenicity. First, we immunized wild-type mice with human COL17NC16a protein. We cultured the splenocytes obtained from the immunized mice with antigen stimulation using NC16a peptide. Then, we subjected the lymphocytes to limiting dilution assay and established 5 COL17-reactive CD4+ T cell clones. To prove the pathogenicity, T cell clones and NC16a-primed B cells were co-transferred into Rag-2-/-/COL17-humanized mice. Recipient mice with some T cell clones and B cells showed erosions and erythemas. Those pathogenic clones also induced IgG deposition at the basement membrane zone, interface change, and eosinophil infiltration. In contrast, the transfer of other clones and B cells failed to induce the BP phenotype. Three of the 5 COL17-reactive T cell clones were regarded as pathogenic and the rest 2 were nonpathogenic. Of note, gene expression analysis revealed that Th2 cytokines were upregulated in the pathogenic clones, especially IL-5. Anti-IL-5 antibody was administered to the recipient mice transferred with pathogenic clones. The anti-IL-5 antibody-treated group tended to show milder skin rash, fewer eosinophil infiltration of skin lesions, and lower circulating anti-COL17NC16a antibody titers compared to the isotype antibody-treated group. In summary, we generated pathogenic COL17-reactive T cell clones, and Th2 cytokine including IL-5 might be involved in the pathogenicity of clones." @default.
- W4366179664 created "2023-04-19" @default.
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- W4366179664 date "2023-05-01" @default.
- W4366179664 modified "2023-09-26" @default.
- W4366179664 title "031 Type XVII collagen-specific CD4+ T cell clones induce bullous pemphigoid in mice by producing IL-5" @default.
- W4366179664 doi "https://doi.org/10.1016/j.jid.2023.03.032" @default.
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