Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity.
Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity.
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DOI：
10.1084/jem.20100639
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发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Allison JP
中科院分区：
文献类型：
--
作者：
Wei J;Loke P;Zang X;Allison JP
B7x的组织特异性表达对自身免疫具有保护作用。B7x是B7/CD28超家族的抑制性成员，在广泛的非造血器官中高度表达，提示B7x在维持外周耐受中发挥作用。由于内源性B7x蛋白在胰岛中表达，我们研究了该分子是否抑制糖尿病的反应。将致病的BDC2.5T细胞转移到B7x缺陷小鼠体内会导致比野生型动物更具侵袭性的糖尿病。这种疾病的恶化与更高频率的胰岛浸润Th1和Th17细胞相关。相反，局部B7x的过度表达抑制了自身免疫的发展，因为将易患糖尿病的BDC2.5/B6G7小鼠与胰岛中过表达B7x的动物杂交可以消除疾病诱导。这种保护是通过抑制CD4T细胞产生干扰素-γ，而不是由于Th2型细胞或调节性T细胞的倾斜或扩张所致。B7x的抑制功能也得到了另一种自身免疫模型-实验性自身免疫性脑脊髓炎的观察支持，在该模型中，与野生型动物相比，B7x缺陷小鼠的疾病恶化。对中枢神经系统渗入的免疫细胞的分析表明，内源性B7x的丢失导致Th1和Th17反应的扩大。来自这两个自身免疫模型的数据提供了证据，表明B7x在外周表达充当免疫检查点，以防止组织特异性自身免疫。
Tissue-specific expression of B7x protects against autoimmunity. B7x, an inhibitory member of the B7/CD28 superfamily, is highly expressed in a broad range of nonhematopoietic organs, suggesting a role in maintaining peripheral tolerance. As endogenous B7x protein is expressed in pancreatic islets, we investigated whether the molecule inhibits diabetogenic responses. Transfer of disease-inducing BDC2.5 T cells into B7x-deficient mice resulted in a more aggressive form of diabetes than in wild-type animals. This exacerbation of disease correlated with higher frequencies of islet-infiltrating Th1 and Th17 cells. Conversely, local B7x overexpression inhibited the development of autoimmunity, as crossing diabetes-susceptible BDC2.5/B6g7 mice to animals overexpressing B7x in pancreatic islets abrogated disease induction. This protection was caused by the inhibition of IFN-γ production by CD4 T cells and not to a skewing or expansion of Th2 or regulatory T cells. The suppressive function of B7x was also supported by observations from another autoimmune model, experimental autoimmune encephalomyelitis, in which B7x-deficient mice developed exacerbated disease in comparison with wild-type animals. Analysis of central nervous system–infiltrating immune cells revealed that the loss of endogenous B7x resulted in expanded Th1 and Th17 responses. Data from these two autoimmune models provide evidence that B7x expression in the periphery acts as an immune checkpoint to prevent tissue-specific autoimmunity.
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B7-1和B7-2共刺激配体的比较分析：表达和功能。
DOI：
10.1084/jem.180.2.631
发表时间：
1994-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hathcock KS;Laszlo G;Pucillo C;Linsley P;Hodes RJ
通讯作者：
Hodes RJ
影响因子：
5.4
作者：
BENNUN, A;OTMY, H;COHEN, IR
通讯作者：
COHEN, IR
影响因子：
15.3
作者：
Herman, AE;Freeman, GJ;Benoist, C
通讯作者：
Benoist, C
影响因子：
56.9
作者：
KATZ, JD;BENOIST, C;MATHIS, D
通讯作者：
MATHIS, D
影响因子：
5.4
作者：
Mensah-Brown, EPK;Shahin, A;Lukic, ML
通讯作者：
Lukic, ML