Date: Sunday, November 5, 2017
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Emerging data suggest that a single microRNA (miR) can profoundly alter the phenotype and outcome of immune responses, offering the prospect of therapeutic use. We recently reported a novel Th17 regulator miR-10b-5p that is present in Th17 cells from patients with Ankylosing Spondylitis (AS). IL-22 is closely related to Th17 cells and also regulated by IL-23, a key cytokine for IL-17A production. Moreover, IL-22 has been implicated in the regulation of new bone formation in experimental models. Therefore, we wonder whether miR-10b-5p affects IL-22 production in AS.
Primary CD4+ T cells were negatively isolated from PBMCs from AS patients (Miltenyi Biotec). Transfection was performed with the Neon transfection system (Thermos Fisher Scientific, Germany) according to manufacturer’s instructions.
The transfection efficiency was evaluated by monitoring FAM (Fluorescein) positive cells using flow cytometry, and qPCR at 24 h after transfection. miR-10b-5p function was determined by overexpression of miR mimic in CD4+ T cells followed by intracellular cytokine staining, cytokine measurement, and qPCR. Statistical analysis was performed using Prism 5.0 Software (GraphPad Software, San Diego, USA). A p < 0.05 was considered statistically significant.
Overexpression of miR-10b-5p reduced both IL-22+CD4+ T cell frequencies and IL-22 production in CD4+ T cells from patients with AS. To identify the cellular targets of miR-10b-5p, we previously performed RNA-sequencing of CD4+ T cells transfected with miR-10b-5p together with in silico Target Scan analysis. MAP3K7 was selected as a target gene because of its known role in cytokine regulation. We then silenced MAP3K7 in CD4+ T cells using siRNA and found the suppression of IL-22 response, mimicking the effect of miR-10b-5p overexpression.
Our data suggest that miR-10b-5p suppress IL-22 production by targeting MAP3K7. miR-10b-5p might be a potential therapeutic candidate for regulation of new bone formation in patients with AS.
To cite this abstract in AMA style:Kim TJ, Jin SH, Chen L, Al-Mossawi MH, Ridley A, Sekine T, Simone D, Shi H, Penkava F, Bowness P. Mir-10b-5p Is a IL-22 Regulator in CD4+T Cells from Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/mir-10b-5p-is-a-il-22-regulator-in-cd4t-cells-from-ankylosing-spondylitis/. Accessed September 24, 2021.
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