L-arginine metabolism in myeloid cells controls T-lymphocyte functions
L-arginine metabolism in myeloid cells controls T-lymphocyte functions
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DOI：
10.1016/s1471-4906(03)00132-7
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发表时间：
2003-06-01
影响因子：
16.8
通讯作者：
Zanovello, P
中科院分区：
文献类型：
--
作者：
Bronte, V;Serafini, P;Zanovello, P
虽然目前的注意力集中在调节性T淋巴细胞作为自身免疫反应的抑制因子，但强大的免疫抑制也由在免疫应激期间进入淋巴器官和外周组织的髓样细胞亚群介导。如果这些骨髓抑制细胞（MSC）从淋巴器官中的活化T淋巴细胞接收信号，它们就会阻止T细胞增殖。MSC使用两种参与精氨酸代谢的酶来控制T细胞反应：诱导型一氧化氮合酶（NOS 2），其产生一氧化氮（NO）和精氨酸酶1（Arg 1），其消耗精氨酸的环境。Th1细胞因子诱导NOS2，而Th2细胞因子上调Arg1。单独诱导任一种酶导致T细胞增殖的可逆阻断。当两种酶一起诱导时，在限制精氨酸的条件下由NOS 2产生的过氧亚硝酸盐导致活化的T淋巴细胞发生凋亡。因此，NOS 2和Arg 1可能在体内单独或协同作用，以控制特定类型的T细胞反应，这些酶的选择性拮抗剂可能证明有益于对抗T细胞反应被不适当抑制的疾病。这一意见是第二次在一系列的调节免疫系统的代谢途径。
Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses, powerful immunosuppression is also mediated by a subset of myeloid cells that enter the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs, they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2), which generates nitric oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1 cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together, peroxynitrites, generated by NOS2 under conditions of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus, NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses, and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the second in a series on the regulation of the immune system by metabolic pathways.