Human TH17 cells express a functional IL-13 receptor and IL-13 attenuates IL-17A production.
Human TH17 cells express a functional IL-13 receptor and IL-13 attenuates IL-17A production.
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DOI：
10.1016/j.jaci.2010.11.043
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Peebles RS Jr
中科院分区：
文献类型：
--
作者：
Newcomb DC;Boswell MG;Zhou W;Huckabee MM;Goleniewska K;Sevin CM;Hershey GK;Kolls JK;Peebles RS Jr
IL-13是变应性气道炎症中气道反应性和粘液表达的中心介质，并且IL-13目前是哮喘的治疗靶点。然而，关于IL-13如何调节人CD 4 + T细胞谱系知之甚少，因为IL-13受体α1（IL-13 R α1），IL-13受体的一个亚基，以前没有报道存在于人T细胞上。确定人CD 4 + Th 17细胞是否表达IL-13 R α1以及IL-13是否调节Th 17细胞因子的产生。从全血中分离幼稚人CD 4+细胞，用抗CD 3和抗CD 28活化，并在IL-13（0- 10 ng/ml）存在下极化为Th 1、Th 2、Th 17或诱导的T调节细胞。Th 17极化后四天检查细胞上清液、总RNA或总蛋白。Th 17细胞表达IL-13 R α1，而Th 0、Th 1、Th 2及诱导性调节性T细胞不表达。IL-13减弱了Th 17极化细胞中IL-17 A的产生以及RORC 2、Runx 1和IRF-4的表达。IL-13既不抑制Th 1细胞产生IFN-γ，也不抑制Th 2细胞产生IL-4。此外，IL-17 A产生的衰减仅在IL-13存在于T细胞活化的24小时内或在再刺激时发生。IL-13 R α1在人CD 4 + Th 17细胞上表达，IL-13在极化和再刺激时减弱IL-17 A的产生。虽然IL-13是减少哮喘相关症状的有吸引力的治疗靶点，但这些结果表明，抑制IL-13产生的疗法可能通过增加IL-17 A产生而产生不良副作用。
IL-13 is a central mediator of airway responsiveness and mucus expression in allergic airway inflammation and IL-13 is currently a therapeutic target for asthma. However, little is known about how IL-13 regulates human CD4+ T cell lineages because the IL-13 receptor α1 (IL-13Rα1), a subunit of the IL-13 receptor, has not previously been reported to exist on human T cells. To determine if human CD4+ Th17 cells express IL-13Rα1 and if IL-13 regulates Th17 cytokine production. Naïve human CD4+ cells were isolated from whole blood, activated with anti-CD3 and anti-CD28, and polarized to Th1, Th2, Th17, or induced T regulatory cells in the presence of IL-13 (0–10ng/ml). Cell supernatants, total RNA, or total protein was examined four days after Th17 polarization. Th17 cells, but not Th0, Th1, Th2 or induced T regulatory cells, expressed IL-13Rα1. IL-13 attenuated IL-17A production as well as expression of RORC2, Runx1, and IRF-4 in Th17 polarized cells. IL-13 neither inhibited IFN-γ production from Th1 cells nor inhibited IL-4 production from Th2 cells. Furthermore, attenuation of IL-17A production only occurred when IL-13 was present within 24 hours of T cell activation or at the time of restimulation. IL-13Rα1 is expressed on human CD4+ Th17 cells, and IL-13 attenuates IL-17A production at polarization and restimulation. While IL-13 is an attractive therapeutic target for decreasing symptoms associated with asthma, these results suggest that therapies inhibiting IL-13 production could have adverse side effects by increasing IL-17A production.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
30.5
作者：
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
4.4
作者：
McMillan, SJ;Xanthou, G;Lloyd, CM
通讯作者：
Lloyd, CM
DOI：
10.1073/pnas.0600666103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Chen, Zhi;Laurence, Arian;O'Shea, John J.
通讯作者：
O'Shea, John J.
影响因子：
6.1
作者：
Batra, V;Musani, AI;Peters, SP
通讯作者：
Peters, SP