Interleukin 18-independent engagement of interleukin 18 receptor-α is required for autoimmune inflammation
Interleukin 18-independent engagement of interleukin 18 receptor-α is required for autoimmune inflammation
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DOI：
10.1038/ni1377
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发表时间：
2006-09-01
影响因子：
30.5
通讯作者：
Becher, Burkhard
中科院分区：
文献类型：
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作者：
Gutcher, Ilona;Urich, Eduard;Becher, Burkhard
T辅助1型（T（H）1）淋巴细胞被认为是负责器官特异性自身免疫性炎症的主要致病细胞类型。由于白细胞介素18（IL-18）是IL-12促进T（H）1细胞发育的辅助因子，我们研究了IL-18及其受体IL-18 R在自身免疫性中枢神经系统炎症中的作用。与IL-12缺陷小鼠类似，IL-18缺陷小鼠对实验性自身免疫性脑脊髓炎易感。相比之下，IL-18 R α缺陷小鼠对实验性自身免疫性脑脊髓炎具有抗性，表明IL-18以外的IL-18 R α配体参与了致脑炎特性。此外，IL-18 R α在抗原呈递细胞上的参与是产生致病性IL-17产生性T辅助细胞所必需的。因此，对于自身免疫性中枢神经系统炎症，IL-18和T（H）1细胞是必需的，而产生IL-18 R α和IL-17的T辅助细胞是必需的。
T helper type 1 (T(H)1) lymphocytes are considered to be the main pathogenic cell type responsible for organ-specific autoimmune inflammation. As interleukin 18 (IL-18) is a cofactor with IL-12 in promoting T(H)1 cell development, we examined the function of IL-18 and its receptor, IL-18R, in autoimmune central nervous system inflammation. Similar to IL-12-deficient mice, IL-18-deficient mice were susceptible to experimental autoimmune encephalomyelitis. In contrast, IL-18R alpha-deficient mice were resistant to experimental autoimmune encephalomyelitis, indicating involvement of an IL-18R alpha ligand other than IL-18 with encephalitogenic properties. Moreover, engagement of IL-18R alpha on antigen-presenting cells was required for the generation of pathogenic IL-17-producing T helper cells. Thus, IL-18 and T(H)1 cells are dispensable, whereas IL-18R alpha and IL-17-producing T helper cells are required, for autoimmune central nervous system inflammation.