Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection.
Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection.
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DOI：
10.1128/jvi.00600-13
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发表时间：
2013-06
影响因子：
5.4
通讯作者：
Mattapallil JJ
中科院分区：
文献类型：
--
作者：
Bixler SL;Sandler NG;Douek DC;Mattapallil JJ
辅助性T细胞17(Th17)在维持粘膜免疫动态平衡和维持粘膜上皮屏障的完整性方面发挥着重要作用。在人类和猿类免疫缺陷病毒(HIV，SIV)感染过程中，Th17细胞的丢失已被广泛报道。Th17细胞缺乏有效的再繁殖与微生物产物移位介导的慢性免疫激活有关。通过对SIV感染猕猴外周血中纯化的CD4T细胞的体外分析，我们发现IL-17表达的抑制与CD4T细胞中负调控基因PIAS3、SHP2和SOCS3的表达上调有关。在感染早期，Th17表达受抑伴随着血浆中可溶性CD14(SCD14)和脂多糖结合蛋白(LBP)水平的升高。血浆病毒载量而不是sCD14或LBP水平与急性免疫激活有关。此外，我们观察到外周血单核细胞上CD14的表达显著增加，这与IL-23的表达和微生物易位的标志有关。综上所述，我们的结果为与急性SIV发病相关的早期事件提供了新的见解，并提示了在抑制Th17细胞方面发挥作用的其他机制。
T helper 17 (Th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. Loss of Th17 cells has been extensively documented during human and simian immunodeficiency virus (HIV, SIV) infections. The lack of effective repopulation of Th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. Using ex vivo analysis of purified peripheral blood CD4 T cells from SIV infected rhesus macaques we show that the suppression of IL-17 expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed Th17 expression was accompanied by elevated levels of soluble CD14 (sCD14) and LPS binding protein (LBP) in the plasma during early stages of infection. Plasma viral loads rather than sCD14 or LBP levels correlated with acute immune activation. Additionally, we observed a significant increase in the expression of CD14 on peripheral blood monocytes that correlated with IL-23 expression and markers of microbial translocation. Taken together, our results provide new insights into the early events associated with acute SIV pathogenesis and suggest to additional mechanisms playing a role in suppression of Th17 cells.