Ashkar S, Weber G F, Panoutsakopoulou V, Sanchirico M E, Jansson M, Zawaideh S, Rittling S R, Denhardt D T, Glimcher M J, Cantor H
Laboratory for Skeletal Disorders and Rehabilitation, Department of Orthopedic Surgery, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Science. 2000 Feb 4;287(5454):860-4. doi: 10.1126/science.287.5454.860.
Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. Mice deficient in Eta-1 (also called osteopontin) gene expression have severely impaired type-1 immunity to viral infection [herpes simplex virus-type 1 (KOS strain)] and bacterial infection (Listeria monocytogenes) and do not develop sarcoid-type granulomas. Interleukin-12 (IL-12) and interferon-gamma production is diminished, and IL-10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.
细胞介导的（1型）免疫对于抵抗大多数细胞内病原体的免疫保护是必要的，并且在过度时可介导器官特异性自身免疫破坏。缺乏Eta-1（也称为骨桥蛋白）基因表达的小鼠对病毒感染[单纯疱疹病毒1型（KOS株）]和细菌感染（单核细胞增生李斯特菌）的1型免疫严重受损，并且不会形成结节样肉芽肿。白细胞介素-12（IL-12）和干扰素-γ的产生减少，而IL-10的产生增加。Eta-1氨基末端部分与其整合素受体之间的磷酸化依赖性相互作用刺激了IL-12的表达，而与CD44的磷酸化非依赖性相互作用则抑制了IL-10的表达。这些发现确定Eta-1是一种关键细胞因子，通过对巨噬细胞IL-12和IL-10细胞因子表达的差异调节，为有效的1型免疫反应奠定基础。
