Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression.
Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression.
复制标题
DOI：
10.4049/jimmunol.0902023
复制
发表时间：
2010-03-01
期刊：
影响因子：
--
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Ren G;Zhao X;Zhang L;Zhang J;L'Huillier A;Ling W;Roberts AI;Le AD;Shi S;Shao C;Shi Y
由ICAM-1和VCAM-1介导的细胞-细胞粘附对于T细胞活化和白细胞募集到炎症部位是至关重要的，因此在引起有效的免疫应答中起重要作用。然而，我们发现ICAM-1和VCAM-1是间充质干细胞（MSC）介导的免疫抑制的关键。当MSC与T细胞共培养时，在T细胞Ag受体活化的存在下，由于ICAM-1和VCAM-1的表达增加，它们显著上调T细胞的粘附能力。通过比较MSC对各种T细胞亚型的免疫抑制作用和这些粘附分子的表达，我们发现MSC表达ICAM-1和VCAM-1越多，它们表现出的免疫抑制能力越大。此外，发现ICAM-1和VCAM-1可由IFN-γ和炎性细胞因子（TNF-α或IL-1）的同时存在诱导。最后，MSC介导的免疫抑制显着逆转，在体外和体内时，粘附分子的基因删除或功能上的封锁，这证实了细胞间接触的重要性，免疫抑制的MSC。总之，这些发现揭示了一种新的功能，粘附分子的免疫调节间充质干细胞和抗粘附治疗在各种免疫疾病的临床研究提供了新的见解。
Cell–cell adhesion mediated by ICAM-1 and VCAM-1 is critical for T cell activation and leukocyte recruitment to the inflammation site and, therefore, plays an important role in evoking effective immune responses. However, we found that ICAM-1 and VCAM-1 were critical for mesenchymal stem cell (MSC)-mediated immunosuppression. When MSCs were cocultured with T cells in the presence of T cell Ag receptor activation, they significantly upregulated the adhesive capability of T cells due to the increased expression of ICAM-1 and VCAM-1. By comparing the immunosuppressive effect of MSCs toward various subtypes of T cells and the expression of these adhesion molecules, we found that the greater expression of ICAM-1 and VCAM-1 by MSCs, the greater the immunosuppressive capacity that they exhibited. Furthermore, ICAM-1 and VCAM-1 were found to be inducible by the concomitant presence of IFN-γ and inflammatory cytokines (TNF-α or IL-1). Finally, MSC-mediated immunosuppression was significantly reversed in vitro and in vivo when the adhesion molecules were genetically deleted or functionally blocked, which corroborated the importance of cell–cell contact in immunosuppression by MSCs. Taken together, these findings reveal a novel function of adhesion molecules in immunoregulation by MSCs and provide new insights for the clinical studies of antiadhesion therapies in various immune disorders.
登录
查看更多内容
影响因子：
4.4
作者：
Haniffa, Muzlifah A.;Wang, Xiao-Nong;Collin, Matthew P.
通讯作者：
Collin, Matthew P.
影响因子：
--
作者：
Batten, Puspa;Sarathchandra, Padmini;Yacoub, Magdi H.
通讯作者：
Yacoub, Magdi H.
影响因子：
20.3
作者：
Aggarwal, S;Pittenger, MF
通讯作者：
Pittenger, MF
影响因子：
4.8
作者：
Liu, XP;Samouilov, A;Zweier, JL
通讯作者：
Zweier, JL
影响因子：
158.5
作者：
Polman, CH;O'Connor, PW;Sandrock, AW
通讯作者：
Sandrock, AW