MicroRNA-126 Deficiency Affects the Development of Thymus CD4+ Single-Positive Cells through Elevating IRS-1.

Autor: Hu, Lin, Xu, Hualin, Lu, Jia, Zhou, Ya, Chu, Fengyun, Zheng, Wen, Lei, Liangyu, Zhao, Juanjuan, Wang, Hairong, Guo, Mengmeng, Chen, Chao, Xu, Lin
Předmět:
Zdroj: International Archives of Allergy & Immunology; Oct2018, Vol. 177 Issue 3, p207-218, 12p, 1 Diagram, 1 Chart, 4 Graphs
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index