Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease.
Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease.
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DOI：
10.1126/scitranslmed.3000632
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发表时间：
2010-05-19
影响因子：
17.1
通讯作者：
McCune JM
中科院分区：
文献类型：
--
作者：
Favre D;Mold J;Hunt PW;Kanwar B;Loke P;Seu L;Barbour JD;Lowe MM;Jayawardene A;Aweeka F;Huang Y;Douek DC;Brenchley JM;Martin JN;Hecht FM;Deeks SG;McCune JM
人类和猿猴免疫缺陷病毒的发病机制以CD4+ T细胞耗竭和慢性T细胞活化为特征，最终导致艾滋病。CD4+ T辅助细胞（TH）通过不同的免疫细胞功能亚群，包括TH1、TH2、T调节（Treg）和分泌白细胞介素-17 （IL-17）的TH17细胞，提供保护性免疫和免疫调节功能。由于IL-17可以增强宿主对微生物制剂的防御，从而维持粘膜屏障的完整性，TH17细胞的缺失可能促进微生物易位和持续炎症。在这里，我们研究hiv血清阳性受试者，发现进行性疾病与外周血和直肠乙状结肠活检中TH17细胞的损失和免疫抑制性Treg细胞比例的相互增加有关。TH17/Treg平衡的丧失与髓系抗原呈递树突状细胞诱导吲哚胺2,3-双加氧酶1 （IDO1）和血浆微生物产物浓度升高有关。在体外，TH17/Treg平衡的丧失是由IDO代谢的近端色氨酸分解产物3-羟基苯甲酸直接介导的。我们假设IDO的诱导可能是一个关键的启动事件，导致TH17/Treg平衡的逆转，从而维持进行性HIV疾病的慢性炎症状态。
The pathogenesis of human and simian immunodeficiency viruses is characterized by CD4+ T cell depletion and chronic T cell activation, leading ultimately to AIDS. CD4+ T helper (TH) cells provide protective immunity and immune regulation through different immune cell functional subsets, including TH1, TH2, T regulatory (Treg), and interleukin-17 (IL-17)–secreting TH17 cells. Because IL-17 can enhance host defenses against microbial agents, thus maintaining the integrity of the mucosal barrier, loss of TH17 cells may foster microbial translocation and sustained inflammation. Here, we study HIV-seropositive subjects and find that progressive disease is associated with the loss of TH17 cells and a reciprocal increase in the fraction of the immunosuppressive Treg cells both in peripheral blood and in rectosigmoid biopsies. The loss of TH17/Treg balance is associated with induction of indoleamine 2,3-dioxygenase 1 (IDO1) by myeloid antigen-presenting dendritic cells and with increased plasma concentration of microbial products. In vitro, the loss of TH17/Treg balance is mediated directly by the proximal tryptophan catabolite from IDO metabolism, 3-hydroxyanthranilic acid. We postulate that induction of IDO may represent a critical initiating event that results in inversion of the TH17/Treg balance and in the consequent maintenance of a chronic inflammatory state in progressive HIV disease.
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影响因子：
44.1
作者：
通讯作者：
--
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1086/597476
发表时间：
2009-04-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Jiang W;Lederman MM;Hunt P;Sieg SF;Haley K;Rodriguez B;Landay A;Martin J;Sinclair E;Asher AI;Deeks SG;Douek DC;Brenchley JM
通讯作者：
Brenchley JM
影响因子：
29.4
作者：
Gurtner, GJ;Newberry, RD;Stenson, WF
通讯作者：
Stenson, WF