IL-6 Production Through Repression of UBASH3A Gene via Epigenetic Dysregulation of Super-Enhancer in CD4+T Cells in Rheumatoid Arthritis DOI Creative Commons
Kaoru Yamagata, Shingo Nakayamada, Tong Zhang

и другие.

Research Square (Research Square), Год журнала: 2022, Номер unknown

Опубликована: Фев. 24, 2022

Abstract Background. UBASH3A as a negative regulator of T-cell receptors (TCRs) signaling is susceptible factor for rheumatoid arthritis (RA) patients who exhibit immune dysfunction. We studied expression in CD4 + T cells from healthy donors and RA patients, the involvement super-enhancer (SE) control expression, contribution to proinflammatory cytokine production. Methods. The mRNA protein levels were examined by quantitative PCR Western blotting, respectively. Locked nucleic acid was administered inhibit enhancer RNA (eRNA) expression. Factors recruited loci displaying SE architecture chromatin immunoprecipitation. transfected with plasmids, measured cytometric bead array. Results. lower than those donors. reduced eRNA_1 eRNA_3 knockdown. In BTB CNC homology 2 (BACH2), silencing transcription factor, accumulated at cells, whereas SE-defining mediator complex subunit 1 (MED1)/bromodomain 4 (BRD4), did not. However, opposite phenomena observed Although stimulation TCRs expressed on led interleukin (IL)-6 production, over-expression significantly inhibited its Conclusions. Transcription suppressed via epigenetic regulation patients. Decreased lead excessive activation TCR signaling, resulting enhanced production IL-6.

Язык: Английский

IL-6 Production Through Repression of UBASH3A Gene via Epigenetic Dysregulation of Super-Enhancer in CD4+T Cells in Rheumatoid Arthritis DOI Creative Commons
Kaoru Yamagata, Shingo Nakayamada, Tong Zhang

и другие.

Research Square (Research Square), Год журнала: 2022, Номер unknown

Опубликована: Фев. 24, 2022

Abstract Background. UBASH3A as a negative regulator of T-cell receptors (TCRs) signaling is susceptible factor for rheumatoid arthritis (RA) patients who exhibit immune dysfunction. We studied expression in CD4 + T cells from healthy donors and RA patients, the involvement super-enhancer (SE) control expression, contribution to proinflammatory cytokine production. Methods. The mRNA protein levels were examined by quantitative PCR Western blotting, respectively. Locked nucleic acid was administered inhibit enhancer RNA (eRNA) expression. Factors recruited loci displaying SE architecture chromatin immunoprecipitation. transfected with plasmids, measured cytometric bead array. Results. lower than those donors. reduced eRNA_1 eRNA_3 knockdown. In BTB CNC homology 2 (BACH2), silencing transcription factor, accumulated at cells, whereas SE-defining mediator complex subunit 1 (MED1)/bromodomain 4 (BRD4), did not. However, opposite phenomena observed Although stimulation TCRs expressed on led interleukin (IL)-6 production, over-expression significantly inhibited its Conclusions. Transcription suppressed via epigenetic regulation patients. Decreased lead excessive activation TCR signaling, resulting enhanced production IL-6.

Язык: Английский

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