期刊
JOURNAL OF INNATE IMMUNITY
卷 6, 期 1, 页码 89-104出版社
KARGER
DOI: 10.1159/000351605
关键词
Endothelial cells; MICA; Cytokines; NKG2D; Signaling
类别
资金
- l'Agence de Biomedecine and La Societe de Nephrologie
- EU-funded Integrated Project in Life Sciences, Genomics and Biotechnology for Health [LSHB-CT-2006-037377]
- Centre Europeen des Sciences de la Transplantation et Immunotherapie
- Agence Nationale pour la Recherche, and Laboratoire d'Excellence (LabEx) TRANSPLANTEX
- La Societe de Nephrologie
MICA are major histoconnpatibility complex class l-related molecules, expressed by endothelial cells (ECs), that may be targets for alloantibodies and NKG2D-expressing natural killer (NK) and T effector cells in organ allografts. This study shows that basal levels of MICA expressed on vascular ECs is sufficient to functionally modulate the expression and activity of the immunoreceptor NKG2D in allogeneic NK cells. We found that MICA expression is differentially regulated at the EC surface in response to cytokines. TNFa upregulates MICA while IFNy significantly decreases MICA at the EC surface. Both cytokines induce the release of soluble MICA by ECs. Modulation of NKG2D correlates with the MICA level on the EC surface. Glycosylation and metalloproteinase activities account for major post-transcriptional mechanisms controlling MICA level and the function in ECs. Our results indicate that, in addition to the NFKB pathway, the nnitogen-activated protein kinase pathways JNK, ERK1 /2 and p38 are key signaling pathways in the control of MICA by the cytokines. Finally, we show that EC proliferation mediated by FGF-2 or wound healing increases the MICA level. Together, our data suggest that inflammation and proliferation regulate endothelial MICA expression and shedding, enabling ECs to modulate NKG2D activity on effector NK and T cells, and provide further evidence of a role for ECs in immunoregulation. (C) 2013 S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据