PMID- 30048989 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1423-0097 (Electronic) IS - 1018-2438 (Linking) VI - 177 IP - 3 DP - 2018 TI - MicroRNA-126 Deficiency Affects the Development of Thymus CD4+ Single-Positive Cells through Elevating IRS-1. PG - 207-218 LID - 10.1159/000490710 [doi] AB - BACKGROUND: MicroRNA-126 (miR-126), a distinct miRNA family member, has been reported to be involved in the development and function of some types of immune cells. However, the potential role of miR-126 in the development of CD4+ T cells remains to be elucidated. OBJECTIVES: To investigate the potential role of miR-126 in the development of CD4+ T cells in the thymus and explore its significance. METHODS: The relative expression level of miR-126 in thymus CD4+ single-positive (SP) cells was detected by Real-Time PCR assay. The possible change in thymus tissue was assessed by histopathology. The total cell number of thymocytes and the expression of activation-associated molecules including CD62L, CD69, and CD44, as well as proliferation-associated nuclear antigen Ki-67, in CD4+ SP cells were assessed by flow cytometric analysis. The expression of IRS-1 and related signaling pathways including Akt and Erk were determined by flow cytometric analysis. RESULTS: Compared with that in wild-type (WT) mice, the total cell number of thymocytes in miR-126 knockdown (KD) mice increased significantly. Moreover, the proportion and absolute cell number of thymic CD4+ SP cells decreased significantly in miR-126 KD mice. Further analysis showed that the frequencies of activation-associated molecules including CD62L, CD69, and CD44, as well as proliferation-associated nuclear antigen Ki-67 in CD4+ SP cells also changed significantly, respectively. Mechanism aspect, the expression level of IRS-1, a putative target of miR-126, increased significantly in CD4+ SP cells in miR-126 KD mice. Moreover, the expression levels of the signaling molecules phosphorylated (p)-Akt and p-Erk also changed significantly. CONCLUSIONS: Our work is the first to reveal a previously unknown role of miR-126 in the development of CD4+ SP cells in the thymus, which might ultimately benefit studies on development of thymocytes. CI - (c) 2018 S. Karger AG, Basel. FAU - Hu, Lin AU - Hu L AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Xu, Hualin AU - Xu H AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Lu, Jia AU - Lu J AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Zhou, Ya AU - Zhou Y AD - Department of Medical Physics, Zunyi Medical University, Zunyi, China. FAU - Chu, Fengyun AU - Chu F AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Zheng, Wen AU - Zheng W AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Lei, Liangyu AU - Lei L AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Zhao, Juanjuan AU - Zhao J AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Wang, Hairong AU - Wang H AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Guo, Mengmeng AU - Guo M AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Chen, Chao AU - Chen C AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. FAU - Xu, Lin AU - Xu L AD - Special Key Laboratory of Gene Detection & Therapy of Guizhou Provincial Education Department, Zunyi, China. AD - Department of Immunology & Talent Base of Biological Therapy of Guizhou Province, Zunyi Medical University, Zunyi, China. LA - eng PT - Journal Article DEP - 20180726 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, T-Lymphocyte) RN - 0 (CD69 antigen) RN - 0 (Cd44 protein, mouse) RN - 0 (Hyaluronan Receptors) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, mouse) RN - 0 (Ki-67 Antigen) RN - 0 (Lectins, C-Type) RN - 0 (MIRN126 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (Mki67 protein, mouse) RN - 126880-86-2 (L-Selectin) SB - IM MH - Animals MH - Antigens, CD/biosynthesis MH - Antigens, Differentiation, T-Lymphocyte/biosynthesis MH - CD4-Positive T-Lymphocytes/*cytology/*immunology MH - Cell Differentiation/*genetics/immunology MH - Flow Cytometry MH - Hyaluronan Receptors/biosynthesis MH - Insulin Receptor Substrate Proteins/metabolism MH - Ki-67 Antigen/biosynthesis MH - L-Selectin/biosynthesis MH - Lectins, C-Type/biosynthesis MH - Lymphocyte Activation/*genetics/immunology MH - Mice MH - Mice, Knockout MH - MicroRNAs/*genetics MH - Thymocytes/cytology/immunology MH - Thymus Gland/cytology OTO - NOTNLM OT - IRS-1 OT - Knockdown OT - MicroRNA-126 OT - SP cells OT - Thymus EDAT- 2018/07/27 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/07/27 06:00 PHST- 2018/04/03 00:00 [received] PHST- 2018/06/07 00:00 [accepted] PHST- 2018/07/27 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/07/27 06:00 [entrez] AID - 000490710 [pii] AID - 10.1159/000490710 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2018;177(3):207-218. doi: 10.1159/000490710. Epub 2018 Jul 26.