SGK1-induced imbalance of T lymphocyte subsets in childhood asthma

Objective To study the expression of SGK1 in T lymphocytes from pediatric asthma, and the effect of SGK1 on the differentiation of T cells, also to explore the function of SGK1 regulating the differentiation of T subset in pediatric asthma. Methods Twenty-eight children with asthma were recruited in Xi′an children′s hospital and divided into moderate group and severe group according to diagnostic guideline of asthma.The serum levels of IL-4, IL-13 and IL-17A were analyzed by ELISA.The CD4+ T cells from PBMC and naive T cells were selected using magnetic beads.Naive T cells were differentiated in vitro under cytokines.SGK1 expression were analyzed with Real-time PCR.The ability of Th2 and Th17 on secreting IL-4 and IL-17A were detected after SGK1 was inhibited by siRNA.In vivo, shRNA-SGK1 Naive T cells were transferred into the mice asthma models by intravenous injection.The airway inflammation were observed in shRNA-SGK1 Naive T models. Results Compared with healthy children, the serum levels of IL-4、IL-13 and IL-17A increased significantly in the children with asthma.Importantly, the levels of these three cytokines were much higher with the development of asthma.SGK1 were up-regulated remarkably in CD4+ T cells from the children with asthma and were positively correlated with IL-13 and IL-17A.Besides, SGK1 expression increased in the differentiated Th2 and Th17 in vitro, but had no change in the differentiated Th1.The levels of IL-4 and IL-17A associated with Th2 and Th17 decreased after SGK1 was inhibited by siRNA.Similarly, In vivo, the serum levels of IL-13 and IL-17A and airway inflammation were reduced in shRNA-SGK1 Naive T models. Conclusion The over-expression of SGK1 in pediatric asthma enhances the asthma progress by promoting the differentiation of T subsets. Key words: SGK1; T lymphocyte; Differentiation; Cytokine; Asthma