PMID- 28987000 OWN - NLM STAT- MEDLINE DCOM- 20190128 LR - 20240313 IS - 1365-2249 (Electronic) IS - 0009-9104 (Print) IS - 0009-9104 (Linking) VI - 191 IP - 2 DP - 2018 Feb TI - MicroRNA-126 deficiency enhanced the activation and function of CD4(+) T cells by elevating IRS-1 pathway. PG - 166-179 LID - 10.1111/cei.13067 [doi] AB - Recent evidence has shown that microRNA-126 (miR-126) has been involved in the development and function of immune cells, which contributed to the pathogenesis of related clinical diseases. However, the potential role of miR-126 in the development and function of CD4(+) T cells remains largely unknown. Here we first found that the activation and proliferation, as well as the expression of interferon (IFN)-gamma, of CD4(+) T cells from miR-126 knock-down (KD) mice using the miRNA-sponge technique were enhanced significantly in vitro, compared with those in CD4(+) T cells from wild-type (WT) mice. To monitor further the possible effect of miR-126 deficiency on the function of CD4(+) T cells in vivo, we used dextran sulphate sodium (DSS)-induced murine model of acute autoimmune colitis and found that miR-126 deficiency could elevate the pathology of colitis. Importantly, the proportion of CD4(+) T cells in splenocytes increased significantly in miR-126KD mice. Moreover, the expression levels of CD69 and CD44 on CD4(+) T cells increased significantly and the expression level of CD62L decreased significantly. Of note, adoptive cell transfer assay showed that the pathology of colitis was more serious in carboxyfluorescein succinimidyl ester (CFSE)-labelled miR-126KD CD4(+) T cell-transferred group, compared with that in the CFSE-labelled WT CD4(+) T cells transferred group. Consistently, the expression levels of CD69 and CD44 on CFSE(+) cells increased significantly. Furthermore, both the proliferation and IFN-gamma secretion of CFSE(+) cells also increased significantly in the CFSE-labelled miR-126KD CD4(+) T cell-transferred group. Mechanistic evidence showed that the expression of insulin receptor substrate 1 (IRS-1), as a functional target of miR-126, was elevated in CD4(+) T cells from miR-126KD mice, accompanied by altered transduction of the extracellular regulated kinase, protein B (AKT) and nuclear factor kappa B (NF-kappaB) pathway. Our data revealed a novel role in which miR-126 was an intrinsic regulator in the function of CD4(+) T cells, which provided preliminary basis for exploring further the role of miR-126 in the development, function of CD4(+) T cells and related clinical diseases. CI - (c) 2017 British Society for Immunology. FAU - Chu, F AU - Chu F AUID- ORCID: 0000-0002-8362-4622 AD - Special Key Laboratory of Gene Detection and Therapy of Guizhou Provincial Education Department, Guizhou, China. AD - Department of Immunology, Zunyi Medical College, Guizhou, China. FAU - Hu, Y AU - Hu Y AD - Special Key Laboratory of Gene Detection and Therapy of Guizhou Provincial Education Department, Guizhou, China. AD - Department of Immunology, Zunyi Medical College, Guizhou, China. FAU - Zhou, Y AU - Zhou Y AD - Department of Medical Physics, Zunyi Medical College, Guizhou, China. FAU - Guo, M AU - Guo M AD - Special Key Laboratory of Gene Detection and Therapy of Guizhou Provincial Education Department, Guizhou, China. AD - Department of Immunology, Zunyi Medical College, Guizhou, China. FAU - Lu, J AU - Lu J AD - Special Key Laboratory of Gene Detection and Therapy of Guizhou Provincial Education Department, Guizhou, China. AD - Department of Immunology, Zunyi Medical College, Guizhou, China. FAU - Zheng, W AU - Zheng W AD - Special Key Laboratory of Gene Detection and Therapy of Guizhou Provincial Education Department, Guizhou, China. AD - Department of Immunology, Zunyi Medical College, Guizhou, China. FAU - Xu, H AU - Xu H AD - Special Key Laboratory of Gene Detection and Therapy of Guizhou Provincial Education Department, Guizhou, China. AD - Department of Immunology, Zunyi Medical College, Guizhou, China. FAU - Zhao, J AU - Zhao J AD - Special Key Laboratory of Gene Detection and Therapy of Guizhou Provincial Education Department, Guizhou, China. AD - Department of Immunology, Zunyi Medical College, Guizhou, China. FAU - Xu, L AU - Xu L AD - Special Key Laboratory of Gene Detection and Therapy of Guizhou Provincial Education Department, Guizhou, China. AD - Department of Immunology, Zunyi Medical College, Guizhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171030 PL - England TA - Clin Exp Immunol JT - Clinical and experimental immunology JID - 0057202 RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, mouse) RN - 0 (MIRN126 microRNA, mouse) RN - 0 (MicroRNAs) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Animals MH - CD4-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Colitis/genetics/*immunology MH - Dextran Sulfate MH - Disease Models, Animal MH - Female MH - Humans MH - Insulin Receptor Substrate Proteins/*metabolism MH - Lymphocyte Activation MH - Mice MH - Mice, Inbred Strains MH - Mice, Knockout MH - MicroRNAs/*genetics MH - Signal Transduction PMC - PMC5758368 OTO - NOTNLM OT - CD4+ T cell OT - DSS OT - IRS-1 OT - cytokines OT - miR-126 EDAT- 2017/10/08 06:00 MHDA- 2019/01/29 06:00 PMCR- 2019/02/01 CRDT- 2017/10/08 06:00 PHST- 2017/09/29 00:00 [accepted] PHST- 2017/10/08 06:00 [pubmed] PHST- 2019/01/29 06:00 [medline] PHST- 2017/10/08 06:00 [entrez] PHST- 2019/02/01 00:00 [pmc-release] AID - CEI13067 [pii] AID - 10.1111/cei.13067 [doi] PST - ppublish SO - Clin Exp Immunol. 2018 Feb;191(2):166-179. doi: 10.1111/cei.13067. Epub 2017 Oct 30.