Regulatory T Cell-Mediated Suppression of Inflammation Induced by DR3 Signaling Is Dependent on Galectin-9.
Regulatory T Cell-Mediated Suppression of Inflammation Induced by DR3 Signaling Is Dependent on Galectin-9.
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DOI：
10.4049/jimmunol.1700575
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发表时间：
2017-10-15
期刊：
影响因子：
--
通讯作者：
Croft M
中科院分区：
文献类型：
--
作者：
Madireddi S;Eun SY;Mehta AK;Birta A;Zajonc DM;Niki T;Hirashima M;Podack ER;Schreiber TH;Croft M
已显示几种TNF受体家族蛋白的刺激通过增加调节性T细胞（Treg）的数量和/或活性来抑制鼠模型中的炎性疾病。我们最近发现一种分子4-1BB利用与半乳糖凝集素9的结合来发挥其免疫抑制作用并驱动CD 8 + Foxp 3 − Treg的扩增。我们现在表明，另一个TNFR家族分子DR 3的连接也需要半乳糖凝集素-9，DR 3以前被发现可以强烈扩增CD 4 + Foxp 3 + Treg并抑制炎症。我们发现DR 3的胞外区直接结合半乳糖凝集素-9，并且半乳糖凝集素-9与Treg中的DR 3缔合。从半乳糖凝集素-9-/-CD 4 + T细胞和Treg的体外研究中，我们发现连接DR 3诱导的刺激活性部分依赖于半乳糖凝集素-9。在体内，在EAE模型中，我们发现DR 3激动剂抑制疾病，与CD 4 + Foxp 3 + Treg细胞的扩增相关，并且这种保护作用在Galectin-9−/−小鼠中丧失。在过敏性肺部炎症模型中观察到类似的结果。因此，我们证明了半乳糖凝集素-9在促进与Treg介导的抑制相关的DR 3活性方面的新功能。
Stimulation of several TNF receptor family proteins has been shown to dampen inflammatory disease in murine models through augmenting the number and/or activity of regulatory T cells (Treg). We recently found that one molecule, 4-1BB, utilized binding to Galectin-9 to exert its immunosuppressive effects and drive expansion of CD8+Foxp3− Treg. We now show that ligation of another TNFR family molecule, DR3, which has previously been found to strongly expand CD4+Foxp3+ Treg and suppress inflammation, also requires Galectin-9. We found that the extracellular region of DR3 directly binds to Galectin-9, and that Galectin-9 associates with DR3 in Treg. From studies in vitro with Galectin-9−/− CD4+ T cells and Treg, we found that stimulatory activity induced by ligating DR3 was in part dependent on Galectin-9. In vivo, in a model of EAE we show that an agonist of DR3 suppressed disease, correlating with expansion of CD4+Foxp3+ Treg cells, and this protective effect was lost in Galectin-9−/− mice. Similar results were seen in an allergic lung inflammation model. Thus, we demonstrate a novel function of Galectin-9 in facilitating activity of DR3 related to Treg-mediated suppression.
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DOI：
10.1159/000289201
发表时间：
2010
期刊：
Current directions in autoimmunity
影响因子：
--
作者：
Chen X;Oppenheim JJ
通讯作者：
Oppenheim JJ
DOI：
10.1084/jem.20132687
发表时间：
2014-06-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Madireddi S;Eun SY;Lee SW;Nemčovičová I;Mehta AK;Zajonc DM;Nishi N;Niki T;Hirashima M;Croft M
通讯作者：
Croft M
影响因子：
3.7
作者：
Oomizu S;Arikawa T;Niki T;Kadowaki T;Ueno M;Nishi N;Yamauchi A;Hattori T;Masaki T;Hirashima M
通讯作者：
Hirashima M
影响因子：
32.4
作者：
Meylan, Francoise;Davidson, Todd S.;Siegel, Richard M.
通讯作者：
Siegel, Richard M.
影响因子：
3.7
作者：
Lv K;Zhang Y;Zhang M;Zhong M;Suo Q
通讯作者：
Suo Q