Stanniocalcin-2 contributes to mesenchymal stromal cells attenuating murine contact hypersensitivity mainly via reducing CD8(+) Tc1 cells.
Stanniocalcin-2 contributes to mesenchymal stromal cells attenuating murine contact hypersensitivity mainly via reducing CD8(+) Tc1 cells.
复制标题
Stanniocalcin-2 主要通过减少 CD8( ) Tc1 细胞来促进间充质基质细胞减轻小鼠接触超敏反应。
DOI：
10.1038/s41419-018-0614-x
复制
发表时间：
2018-05-01
影响因子：
9
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Chen X;Liu Q;Huang W;Cai C;Xia W;Peng Y;Zheng S;Li G;Xu Y;Wang J;Liu C;Zhang X;Huang L;Xiang AP;Zhang Q
间充质基质细胞(MSCs)被证明可以改善变态反应性接触性皮炎(ACD)，这是一种典型的T细胞介导的疾病。然而，基于MSC的ACD治疗背后的潜在机制尚未完全阐明。Stanniocalcins(STCs)由一系列分泌的糖蛋白激素组成，这些激素是重要的抗炎蛋白。在这里，我们研究了STCs在MSC介导的T细胞抑制中的作用，以及它们在基于MSC的ACD治疗中的潜在作用。基因表达谱显示，在MSCs中高表达STC2，而不是STC1。MSCs中STC2基因的敲除显著削弱了它们减少产生肿瘤坏死因子-α和干扰素-γ的CD8+T细胞的作用。重要的是，抑制MSCs中STC2的表达减弱了其对小鼠接触性超敏反应的治疗作用，主要是恢复了产生干扰素-γ的CD8+T细胞(Tc1细胞)的产生和渗透。机制上，STC2与血红素加氧酶1(HO-1)共定位于MSCs，并通过调节HO-1活性参与MSC介导的CD8+Tc1细胞减少。综上所述，这些发现重新确认STC2是第一个负责介导MSCs对同种异体T细胞的免疫调节作用的锡钙素，STC2主要通过减少CD8+Tc1细胞来参与基于MSC的ACD治疗。
Mesenchymal stromal cells (MSCs) have been demonstrated to ameliorate allergic contact dermatitis (ACD), a typical T-cell-mediated disorder. However, the underlying mechanisms behind the MSC-based treatment for ACD have not yet been fully elucidated. The stanniocalcins (STCs) comprise a family of secreted glycoprotein hormones that act as important anti-inflammatory proteins. Here, we investigated the roles of STCs in MSC-mediated T-cell suppression and their potential role in the MSC-based treatment for ACD. Gene expression profiling revealed that STC2, but not STC1, was highly expressed in MSCs. STC2 knockdown in MSCs significantly impaired their effects in reducing TNF-α- and IFN-γ-producing CD8+ T cells. Importantly, silencing the STC2 expression in MSCs abated their therapeutic effect on contact hypersensitivity (CHS) in mice, mainly restoring the generation and infiltration of IFN-γ-producing CD8+ T cells (Tc1 cells). Mechanistically, STC2 co-localized with heme oxygenase 1 (HO-1) in MSCs, and contributed to MSC-mediated reduction of CD8+ Tc1 cells via regulating HO-1 activity. Together, these findings newly identify STC2 as the first stanniocalcin responsible for mediating the immunomodulatory effects of MSCs on allogeneic T cells and STC2 contribute to MSC-based treatment for ACD mainly via reducing the CD8+ Tc1 cells.
登录
查看更多内容
影响因子：
50.3
作者：
Di Biase S;Lee C;Brandhorst S;Manes B;Buono R;Cheng CW;Cacciottolo M;Martin-Montalvo A;de Cabo R;Wei M;Morgan TE;Longo VD
通讯作者：
Longo VD
DOI：
10.1152/ajprenal.00138.2003
发表时间：
2004-02-01
影响因子：
4.2
作者：
Kanellis, J;Bick, R;Sheikh-Hamad, D
通讯作者：
Sheikh-Hamad, D
影响因子：
6
作者：
Huang, Luping;Garcia, Gabriela;Sheikh-Hamad, David
通讯作者：
Sheikh-Hamad, David
影响因子：
5.2
作者：
Kim, Hyung-Sik;Lee, Ji Hyun;Kim, Tae-Yoon
通讯作者：
Kim, Tae-Yoon
影响因子：
13.8
作者：
Eichenfield, Lawrence F.;Tom, Wynnis L.;Berger, Timothy G.;Krol, Alfons;Paller, Amy S.;Schwarzenberger, Kathryn;Bergman, James N.;Chamlin, Sarah L.;Cohen, David E.;Cooper, Kevin D.;Cordoro, Kelly M.;Davis, Dawn M.;Feldman, Steven R.;Hanifin, Jon M.;Margolis, David J.;Silverman, Robert A.;Simpson, Eric L.;Williams, Hywel C.;Elmets, Craig A.;Block, Julie;Harrod, Christopher G.;Begolka, Wendy Smith;Sidbury, Robert
通讯作者：
Sidbury, Robert