CTLA-4-Ig regulates tryptophan catabolism in vivo
CTLA-4-Ig regulates tryptophan catabolism in vivo
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DOI：
10.1038/ni846
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发表时间：
2002-11-01
影响因子：
30.5
通讯作者：
Puccetti, P
中科院分区：
文献类型：
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作者：
Grohmann, U;Orabona, C;Puccetti, P
细胞毒性T淋巴细胞相关抗原4（CTLA-4）在外周耐受中起着关键作用。然而，由CTLA-4与抗原呈递细胞上表达的B7反配体相互作用引发的调节途径尚未完全了解。我们在这里表明，由可溶性融合蛋白CTLA-4-免疫球蛋白（CTLA-4-IG）诱导的胰岛移植物的长期存活取决于宿主中有效的色氨酸催化剂。在体外，我们表明CTLA-4-IG调节表达B37的树突状细胞中细胞因子依赖性的色氨酸分解代谢。这些数据表明，色氨酸催化剂的调节是CTLA-4在体内发挥功能的一种手段，CTLA-4作为B7受体分子的配体发挥作用，B7受体分子抑制细胞内信号。
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a critical role in peripheral tolerance. However, regulatory pathways initiated by the interactions of CTLA-4 with B7 counterligands expressed on antigen-presenting cells are not completely understood. We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan catabolism in the host. In vitro, we show that CTLA-4-Ig regulates cytokine-dependent tryptophan catabolism in B37-expressing dendritic cells. These data suggest that modulation of tryptophan catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals.