Lumican negatively controls the pathogenicity of murine encephalitic TH17 cells.
Lumican negatively controls the pathogenicity of murine encephalitic TH17 cells.
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DOI：
10.1002/eji.201646507
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发表时间：
2016-12
影响因子：
5.4
通讯作者：
Yang, Xuexian O.
中科院分区：
文献类型：
--
作者：
Castillo, Eliseo F.;Zheng, Handong;Van Cabanlong, Christian;Dong, Fei;Luo, Yan;Yang, Yi;Liu, Meilian;Kao, Winston W. -Y.;Yang, Xuexian O.
TH 17细胞在人类多发性硬化和动物实验性自身免疫性脑脊髓炎（EAE）的发展中起重要作用。然而，在自身免疫性神经炎症中，TH 17细胞的致病性是如何被控制的还不清楚。在体外实验中，我们发现细胞外基质蛋白Lumican（Lum）在小鼠TH细胞亚群中选择性表达。Lum缺乏导致实验性自身免疫性脑脊髓炎的早期发作和严重程度的增强。这种在Lm缺陷小鼠中增强的疾病与IL-17和IL-21的产生增加和TH 17细胞凋亡减少有关。细胞因子产生的失调似乎对TH 17细胞特异，因为TH 1和TH 2细胞极化和/或细胞因子产生未改变。此外，与对照组相比，源自Lum缺陷小鼠的MOG特异性TH 17细胞的过继转移导致更早的发病和疾病严重程度的增加，突出了Lum的TH 17细胞内在效应。综上所述，我们的研究结果表明，Lum负调节脑炎TH 17细胞，暗示TH 17细胞介导的自身免疫性和炎症性疾病的潜在治疗途径。
TH17 cells play an essential role in the development of both human multiple sclerosis and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, it is not well understood how the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation. In vitro, we found Lumican (Lum), an extracellular matrix protein, is selectively expressed by TH17 cells among tested murine TH subsets. Lum-deficiency leads to earlier onset and enhanced severity of experimental autoimmune encephalomyelitis. This enhanced disease in Lum-deficient mice is associated with increased production of IL-17 and IL-21 and decreased TH17 cell apoptosis. Dysregulation in cytokine production appears to be specific to TH17 cells as TH1 and TH2 cell polarization and/or cytokine production were unaltered. Furthermore, adoptive transfer of MOG-specific TH17 cells derived from Lum-deficient mice led to earlier onset and increased severity of disease compared to controls highlighting a TH17 cell-intrinsic effect of Lum. Taken together, our results suggest that Lum negatively regulates encephalitic TH17 cells, implicating a potential therapeutic pathway in TH17 cell-mediated autoimmune and inflammatory diseases.
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