CD1d-dependent natural killer T cells attenuate angiotensin II-induced cardiac remodelling via IL-10 signalling in mice
CD1d-dependent natural killer T cells attenuate angiotensin II-induced cardiac remodelling via IL-10 signalling in mice
复制标题
CD1d 依赖性自然杀伤 T 细胞通过 IL-10 信号传导减弱小鼠血管紧张素 II 诱导的心脏重塑。
DOI：
10.1093/cvr/cvy164
复制
发表时间：
2019-01-01
影响因子：
10.8
通讯作者：
Li, Hui-Hua
中科院分区：
文献类型：
--
作者：
Wang, Hong-Xia;Li, Wen-Jun;Li, Hui-Hua
Aims CD1d is a member of the cluster of differentiation 1 (CD1) family of glycoproteins expressed on the surface of various antigen-presenting cells, which is recognized by natural killer T (NKT) cells. CD1d-dependent NKT cells play an important role in immune-mediated diseases; but the role of these cells in regulating cardiac remodelling remains unknown.Methods and results Cardiac remodelling was induced by angiotensin (Ang) II infusion for 2weeks. Ang II-induced increase in hypertension, cardiac performance, hypertrophy and fibrosis, inflammatory response, and activation of the NF-kB and TGF-1/Smad2/3 pathways was significantly aggravated in CD1d knockout (CD1dko) mice compared with wild-type (WT) mice, but these effects were markedly abrogated in WT mice treated with -galactosylceramide (GC), a specific activator of NKT cells. Adoptive transfer of CD1dko bone marrow cells to WT mice further confirmed the deleterious effect of CD1dko. Moreover, IL-10 expression was significantly decreased in CD1dko hearts but increased in GC-treated mice. Co-culture experiments revealed that CD1dko dendritic cells significantly reduced IL-10 mRNA expression from NKT cells. Administration of recombinant murine IL-10 to CD1dko mice improved hypertension, cardiac performance, and adverse cardiac remodelling induced by Ang II, and its cardioprotective effect was possibly associated with activation of STAT3, and inhibition of the TGF-1 and NF-kB pathways.Conclusion These findings revealed a previously undefined role for CD1d-dependent NKT cells in Ang II-induced cardiac remodelling, hence activation of NKT cells may be a novel therapeutic target for hypertensive cardiac disease.
