IDO activates regulatory T cells and blocks their conversion into Th17-like T cells.
IDO activates regulatory T cells and blocks their conversion into Th17-like T cells.
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DOI：
10.4049/jimmunol.0900986
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发表时间：
2009-08-15
期刊：
影响因子：
--
通讯作者：
Mellor AL
中科院分区：
文献类型：
--
作者：
Baban B;Chandler PR;Sharma MD;Pihkala J;Koni PA;Munn DH;Mellor AL
TLR配体是有效的疫苗佐剂，因为它们刺激强大的促炎和免疫效应器反应，并消除调节性T细胞(Tregs)介导的抑制2。矛盾的是，全身注射高剂量与TLR9配体结合的CpG寡核苷酸(CPGS)刺激小鼠脾中的Tregs，依赖PD-1与其配体之间的相互作用获得强大的抑制活性。这种对CpG处理的反应在几个小时内表现出来，并且是由TLR9结扎后诱导表达免疫抑制酶IDO的罕见的浆细胞样树突状细胞(CD19+pDCs)群介导的。当IDO被阻断时，CpG治疗并没有激活Tregs，而是刺激pDC统一表达促炎细胞因子IL-6，这反过来又重新编程Foxp3系Tregs来表达IL-17。因此，CpG诱导的pDC的IDO活性是一个关键的分子开关，诱导Tregs获得稳定的抑制表型，同时阻断CpG诱导的IL-6的表达，这是重新编程Tregs成为TH17样效应T细胞所必需的。这些发现支持这样的假设，即在生理环境中，IDO主要控制Treg对炎症刺激的功能状态。
TLR ligands are effective vaccine adjuvants because they stimulate robust pro-inflammatory and immune effector responses, and abrogate suppression mediated by regulatory T cells (Tregs)2. Paradoxically, systemic administration of high doses of CpG oligonucleotides (CpGs) that bind to TLR9 ligands stimulated Tregs in mouse spleen to acquire potent suppressor activity dependent on interactions between PD-1 and its ligands. This response to CpG treatment manifested in a few hours, and was mediated by a rare population of plasmacytoid dendritic cells (CD19+ pDCs) induced to express the immunosuppressive enzyme IDO after TLR9 ligation. When IDO was blocked CpG treatment did not activate Tregs, but instead stimulated pDCs to uniformly express the pro-inflammatory cytokine IL-6, which in turn re-programmed Foxp3-lineage Tregs to express IL-17. Thus, CpG-induced IDO activity in pDCs acted as a pivotal molecular switch that induced Tregs to acquire a stable suppressor phenotype, while simultaneously blocking CpG-induced IL-6 expression required to re-program Tregs to become TH17-like effector T cells. These findings support the hypothesis that IDO dominantly controls the functional status of Tregs in response to inflammatory stimuli in physiologic settings.
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影响因子：
4.4
作者：
Baban, B;Hansen, AM;Mellor, AL
通讯作者：
Mellor, AL
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
11.2
作者：
Hou, De-Yan;Muller, Alexander J.;Munn, David H.
通讯作者：
Munn, David H.
DOI：
10.1084/jem.20030633
发表时间：
2003-07-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grohmann U;Fallarino F;Bianchi R;Orabona C;Vacca C;Fioretti MC;Puccetti P
通讯作者：
Puccetti P