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- W4210368850 abstract "Objective: Systemic juvenile idiopathic arthritis (sJIA) features characteristics of autoinflammation and autoimmunity, culminating in chronic arthritis. Previous work indicated decreased IFNg-expression by T helper (Th) cells in sJIA. Here, we hypothesized this to result from aberrant or incomplete Th cell polarization. Methods: Cells or sera were obtained from healthy controls (HC, n=26) and sJIA patients (n=61). Isolated naive Th cells were cultured under Th1, Th17, and T follicular or T peripheral helper (Tf/ph) polarizing conditions and were partly co-cultured with allogenic memory B cells. Surface marker, transcription factor, and/or cytokine expression in peripheral or polarized Th cells or sera as well as B cellular plasma blast generation were studied by flow cytometry, multiplexed bead array assays, ELISA and retrospective RNA profiling analyses. Results: SJIA naive Th cell differentiation towards Th1 resulted in low IFNg; and Eomesodermin expression. Instead, developing sJIA Th1 cells revealed elevated IL-21 release that negatively correlated with cellular IFNg; and Eomesodermin expression. Both In vitro and ex vivo, IL-21 together with PD-1, ICOS and CXCR5 expression indicated naive sJIA Th cell differentiation to rather polarize towards a Tf/ph phenotype. Retrospective analysis of whole blood RNA sequencing data demonstrated sJIA-specific overexpression of Bcl-6 as respective master transcription factor. Compared to controls, in vitro generated sJIA Tf/ph cells promoted enhanced B cellular plasma-blast generation. Conclusion: In sJIA pathogenesis skewing of sJIA naive Th cell differentiation towards a Tf/ph phenotype may represent an echo of autoimmunity, which could shed light on the mechanisms driving the progression towards chronic destructive arthritis." @default.
- W4210368850 created "2022-02-08" @default.
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- W4210368850 date "2022-02-02" @default.
- W4210368850 modified "2023-09-26" @default.
- W4210368850 title "Aberrant naive CD4+ T Cell differentiation in systemic juvenile idiopathic arthritis is committed to B cell help" @default.
- W4210368850 doi "https://doi.org/10.1101/2022.02.01.22270100" @default.
- W4210368850 hasPublicationYear "2022" @default.
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