Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
J Immunol. 2013 Jul 1;191(1):154-63. doi: 10.4049/jimmunol.1203016. Epub 2013 May 29.
The TNF superfamily ligand LIGHT (lymphotoxin-like, exhibits inducible expression and competes with HSV glycoprotein D for herpesvirus entry mediator [HVEM], a receptor expressed by T lymphocytes) has been shown to play a role in T cell costimulation and be involved in apoptosis of mononuclear cells. As both T cells and monocytes are key components in the development and progression of experimental autoimmune encephalomyelitis (EAE), we studied the role of LIGHT in EAE. Following immunization with myelin oligodendrocyte glycoprotein peptide (35-55), LIGHT-deficient mice developed severe EAE that resulted in an atypically high mortality rate. Histological examinations revealed intensive activation of microglia/macrophages in the CNS and higher numbers of apoptotic cells within the CNS parenchyma of LIGHT-deficient mice. However, myelin oligodendrocyte glycoprotein peptide-specific CD4(+) T cells from LIGHT-deficient mice showed reduced IFN-γ and IL-17 production and migration. Serum levels of reactive nitrogen intermediates and CNS transcripts of several proinflammatory cytokines and chemokines were also substantially decreased in the absence of LIGHT. EAE adoptive transfer experiments and bone marrow chimeras indicated that expression of LIGHT on donor cells is not required for disease induction. However, its expression on CNS host cells is a decisive factor to limit disease progression and tissue damage. Together, these data show that LIGHT expression is crucially involved in controlling activated macrophages/microglia during autoimmune CNS inflammation.
TNF 超家族配体 LIGHT（淋巴毒素样，诱导表达并与 HSV 糖蛋白 D 竞争疱疹病毒进入介体 [HVEM]，HVEM 是 T 淋巴细胞表达的受体）已被证明在 T 细胞共刺激中发挥作用，并参与单核细胞的凋亡。由于 T 细胞和单核细胞都是实验性自身免疫性脑脊髓炎 (EAE) 发展和进展的关键组成部分，我们研究了 LIGHT 在 EAE 中的作用。在用髓鞘少突胶质细胞糖蛋白肽 (35-55) 免疫后，缺乏 LIGHT 的小鼠发生严重的 EAE，导致异常高的死亡率。组织学检查显示中枢神经系统中小胶质细胞/巨噬细胞的强烈激活和缺乏 LIGHT 的小鼠中枢神经系统实质内凋亡细胞数量增加。然而，缺乏 LIGHT 的小鼠的髓鞘少突胶质细胞糖蛋白肽特异性 CD4(+) T 细胞显示 IFN-γ 和 IL-17 产生和迁移减少。缺乏 LIGHT 时，反应性氮中间产物的血清水平和几种促炎细胞因子和趋化因子的中枢神经系统转录本也显著降低。EAE 被动转移实验和骨髓嵌合体表明，供体细胞上 LIGHT 的表达对于疾病诱导不是必需的。然而，其在中枢神经系统宿主细胞上的表达是限制疾病进展和组织损伤的决定性因素。总之，这些数据表明 LIGHT 表达在控制自身免疫性中枢神经系统炎症期间激活的巨噬细胞/小胶质细胞中起着至关重要的作用。
