Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells
Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells
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DOI：
10.1002/eji.201142322
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发表时间：
2012-07-01
影响因子：
5.4
通讯作者：
Kang, Chang-Yuil
中科院分区：
文献类型：
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作者：
Lee, Kyoo-A;Song, You Chan;Kang, Chang-Yuil
视黄酸 (RA) 是免疫反应的多种调节剂。尽管 RA 通过增加抗原呈递细胞 (APC) 上的 CD1d 表达来促进自然杀伤 T (NKT) 细胞活化，但 RA 对体内 NKT 细胞反应的直接影响尚不清楚。在本研究中，我们证明了 RA 对 Con A 诱导的肝炎严重程度和 NKT 细胞分子变化的影响。首先，我们证明 RA 可改善 Con A 诱导的肝损伤。 RA 调节 IFN-α 的产生，与血清中的细胞因子水平相关。 NKT 细胞可作用于 IL-4，但不作用于 TNF-a，而不影响 NKT 细胞的激活状态。然而，RA 并没有减轻α-GalCer 诱导的肝损伤，尽管它减少了 IFN-γ 的产生。血清中 IL-4 水平而非 TNF-a 水平。当体外用 RA 处理肝单核细胞 (MNC) 或 NKT 杂交瘤细胞时，也检测到这种调节。 RA对NKT细胞的调节作用是由RAR-a介导的，RA降低了MAPK的磷酸化。这些结果表明，RA在肝炎中差异性地调节NKT细胞产生效应细胞因子，并且RA对肝炎的抑制作用随肝损伤的致病机制而变化。
Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen-presenting cells (APCs), the direct effects of RA on NKT-cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A-induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN-? and IL-4 but not TNF-a by NKT cells without influencing the NKT-cell activation status. However, RA did not alleviate a-GalCer-induced liver injury, even though it reduced IFN-? and IL-4 but not TNF-a levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR-a, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.