Reduction of CD19 autoimmunity marker on B cells of paediatric SLE patients through repressing PU.1/TNF-α/BAFF axis pathway by miR-155. (4th May 2017)

• Record Type: Journal Article
• Authors: Aboelenein, H. R.; Hamza, M. T.; Marzouk, H.; Youness, R. A.; Rahmoon, M.; Salah, S.; Abdelaziz, A. I.
• Is Part Of: Growth factors. Volume 35:Number 2/3(2017)
• Page Start: 49
• Page End: 60
• Publication Date: 2017-05-04
• Subjects: microRNA 155 -- BAFF -- PU.1 -- TNF-α -- B cells -- lupus; Growth factors -- Periodicals; Physiology -- Periodicals; 611
• DOI: 10.1080/08977194.2017.1345900
• Languages: English
• ISSNs: 0897-7194

Abstract

Abstract: microRNA-155 (miR-155) is implicated in regulating B-cell activation and survival that is important in systemic lupus erythematosus (SLE) pathogenesis. PU.1, a target for miR-155, is a crucial regulator of B-cell development and enhances Tumour-Necrosis-factor-alpha (TNF-α) expression. TNF-α induces the expression of B-cell-activating-factor (BAFF). BAFF is reported to increase the expression of the autoimmunity marker; CD19. This study aimed to investigate the regulation of expression of PU.1 in pediatric-systemic-lupus-erythematosus (pSLE) patients by miR-155, and hence evaluate its impact on TNF-α/BAFF/CD19 signalling pathway. Screening revealed that PU.1 is upregulated in PBMCs and B-cells of pSLE patients. PU.1 expression directly correlated with systemic-lupus-erythematosus disease-activity-index-2 K SLEDAI-2K. Ectopic expression of miR-155 and knockdown of PU.1 suppressed PU.1, TNF-α and BAFF. Finally, miR-155 decreased the proportion of BAFF-expressing-B-cells and CD19 protein expression. These findings suggest that miR-155 suppresses autoimmunity through transcriptional repression of PU.1 and TNF-α, which in turn suppresses BAFF and CD19 protein expression.