Upregulation of SLAMF3 on human T cells is induced by palmitic acid through the STAT5-PI3K/Akt pathway and features the chronic inflammatory profiles of type 2 diabetes
Upregulation of SLAMF3 on human T cells is induced by palmitic acid through the STAT5-PI3K/Akt pathway and features the chronic inflammatory profiles of type 2 diabetes
复制标题
棕榈酸通过 STAT5-PI3K/Akt 通路诱导人类 T 细胞上 SLAMF3 的上调，并具有 2 型糖尿病的慢性炎症特征
DOI：
10.1038/s41419-019-1791-y
复制
发表时间：
2019-07
影响因子：
9
通讯作者：
Hu Zheng
中科院分区：
文献类型：
--
作者：
Zhou Tong;Wang Guixia;Lyu Yanan;Wang Lei;Zuo Siyao;Zou Jun;Sun Lin;Zhao Wenjie;Shu Chang;Yang Yong Guang;Hu Zheng
代谢应激诱导的低级别慢性炎症在胰岛素抵抗和2型糖尿病（T2D）的发展中起重要作用。新出现的证据强调了在肥胖诱导的代谢应激条件下直接阐明T细胞激活的重要性，因为在这种条件下启动的T细胞被发现获得了独特的表型和功能。在此，我们发现与健康对照相比，T2D患者T细胞上的信号淋巴细胞激活分子家族成员3 （SLAMF3）表达显著上调。重要的是，SLAMF3上调与产生促炎细胞因子的能力增加有关。与不产生细胞因子的T细胞相比，在短时间（4小时）刺激产生IFN-γ或IL-17的T2D患者T细胞中，SLAMF3的表达显著增加。与这一发现一致，slamf3ight细胞比SLAMF3lowT细胞对抗cd3 /CD28抗体的TCR刺激明显更敏感。此外，棕榈酸（PA）处理导致SLAMF3在由抗cd3 /CD28抗体引发的人T细胞和Jurkat细胞（一种人T细胞系）上的显著上调。RNA测序结果显示，在PA启动的T细胞中，PI3K/Akt信号通路被强烈激活。进一步的机制研究表明，抑制PI3K/Akt信号或其上游介质STAT5可以阻止pa诱导的T细胞SLAMF3上调。这些结果表明，在T2D患者中，SLAMF3上调与T细胞活化和细胞因子产生有关，并提示T2D患者中饱和脂肪酸升高可能通过激活STAT5-PI3K/Akt信号通路诱导T细胞上SLAMF3上调。
Metabolic stress-induced low-grade chronic inflammation plays an important role in the development of insulin-resistance and type 2 diabetes (T2D). Emerging evidence highlights the importance of directly elucidating T-cell activation under the obesity-induced metabolic stress condition, as T cells primed under such conditions were found to acquire a unique phenotype and function. Herein, we found a significant upregulation of signaling lymphocytic activation molecule family member 3 (SLAMF3) expression on T cells from T2D patients compared to those of healthy controls. Importantly, SLAMF3 upregulation was associated with an increased ability to produce proinflammatory cytokines. Significantly increased SLAMF3 expression was seen in T2D patient T cells that produce IFN-γ or IL-17 upon short (4-h) stimulation, compared to non-cytokine-producing T cells. In line with this finding, SLAMF3highT cells were significantly more sensitive than SLAMF3lowT cells to TCR stimulation with anti-CD3/CD28 antibodies. Furthermore, treatment with palmitic acid (PA) led to significant upregulation of SLAMF3 on human T cells primed by anti-CD3/CD28 antibodies and on Jurkat cells, a human T-cell line. RNA sequencing revealed strong activation of the PI3K/Akt signaling pathway in T cells that were primed with PA. Further mechanistic studies showed that inhibition of PI3K/Akt signaling, or its upstream mediator STAT5 can prevent PA-induced SLAMF3 upregulation on T cells. These results indicate that SLAMF3 upregulation is associated with T-cell activation and cytokine production in T2D patients, and suggest that elevated saturated fatty acids in T2D patients may induce SLAMF3 upregulation on T cells via activation of the STAT5-PI3K/Akt signaling pathway.
登录
查看更多内容
影响因子：
3.9
作者：
Douiev L;Soiferman D;Alban C;Saada A
通讯作者：
Saada A
影响因子：
48
作者：
Katz, Yarden;Wang, Eric T.;Airoldi, Edoardo M.;Burge, Christopher B.
通讯作者：
Burge, Christopher B.
影响因子：
20.3
作者：
Wofford, Jessica A.;Wieman, Heather L.;Rathmell, Jeffrey C.
通讯作者：
Rathmell, Jeffrey C.
影响因子：
4.4
作者：
Graham, DB;Bell, MP;McKean, DJ
通讯作者：
McKean, DJ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y