Among CXCR3 chemokines, IFN-γ-inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN-γ (CXCL9) imprints a pattern for the subsequent development of autoimmune disease
Among CXCR3 chemokines, IFN-γ-inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN-γ (CXCL9) imprints a pattern for the subsequent development of autoimmune disease
复制标题
DOI：
10.4049/jimmunol.171.12.6838
复制
发表时间：
2003-12-15
影响因子：
4.4
通讯作者：
Oldstone, MBA
中科院分区：
文献类型：
--
作者：
Christen, U;McGavern, DB;Oldstone, MBA
淋巴细胞性脉络丛脑膜炎病毒感染胰腺导致CXCR 3趋化因子快速和差异表达。IFN-γ诱导的10 kDa蛋白（IP-10），与IFN-γ和IFN-诱导的T细胞-α化学引诱物诱导的单核因子相反，在感染后24小时内强烈表达。阻断IP-10而不是IFN-γ诱导的单核因子，可中止胰腺β细胞Ag特异性损伤的严重程度并消除1型糖尿病。在机制上，IP-10阻断阻碍外周Ag特异性T细胞的扩增并阻碍它们迁移到胰腺中。IP-10的表达仅限于感染胰腺并能够引起糖尿病的病毒。因此，病毒诱导的器官特异性自身免疫性疾病可能依赖于病毒的嗜性及其通过选择性诱导趋化因子改变局部环境的能力，所述趋化因子使感染的组织为随后的适应性免疫应答的破坏做好准备。
Infection of the pancreas with lymphocytic choriomeningitis virus results in rapid and differential expression among CXCR3 chemokines. IFN-gamma-inducible protein of 10 kDa (IP-10), in contrast with monokine induced by IFN-gamma and IFN-inducible T cell-alpha chemoattractant, is strongly expressed within 24 h postinfection. Blocking of IP-10, but not monokine induced by IFN-gamma, aborts severity of Ag-specific injury of pancreatic beta cells and abrogates type 1 diabetes. Mechanistically, IP-10 blockade impedes the expansion of peripheral Ag-specific T cells and hinders their migration into the pancreas. IP-10 expression was restricted to viruses infecting the pancreas and that are capable of causing diabetes. Hence, virus-induced organ-specific autoimmune diseases may be dependent on virus tropism and its ability to alter the local milieu by selectively inducing chemokines that prepare the infected tissue for the subsequent destruction by the adaptive immune response.