A defect in tryptophan catabolism impairs tolerance in nonobese diabetic mice.
A defect in tryptophan catabolism impairs tolerance in nonobese diabetic mice.
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DOI：
10.1084/jem.20030633
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发表时间：
2003-07-07
期刊：
影响因子：
--
通讯作者：
Puccetti P
中科院分区：
文献类型：
--
作者：
Grohmann U;Fallarino F;Bianchi R;Orabona C;Vacca C;Fioretti MC;Puccetti P
非肥胖糖尿病（NOD）小鼠发生自身免疫的倾向反映了外周和中枢耐受性的缺陷。在这些小鼠中已经描述了几种缺陷，其中包括异常的抗原呈递细胞功能和过氧亚硝酸盐形成。NOD小鼠中的前驱糖尿病和糖尿病已经通过多种免疫疗法（包括干扰素（IFN）-γ）以不同的结果靶向。这种细胞因子可能有助于特定形式的耐受性，凭借其激活免疫抑制性色氨酸催化剂的能力。在这里，我们提供的证据表明，IFN-γ不能诱导耐受性的树突状细胞从高度易感的雌性小鼠早期糖尿病前期。这种效应与色氨酸催化酶受损有关，与IFN-γ瞬时阻断细胞内信号传导的Stat 1途径有关，并由过氧亚硝酸盐产生引起。然而，过氧亚硝酸盐抑制剂的使用可以挽救色氨酸catenorism和耐受性，在这些小鼠。这是第一次报告的实验性自身免疫性疾病，其中有缺陷的耐受性是因果关系的受损色氨酸催化剂。
The predisposition of nonobese diabetic (NOD) mice to develop autoimmunity reflects deficiencies in both peripheral and central tolerance. Several defects have been described in these mice, among which aberrant antigen-presenting cell function and peroxynitrite formation. Prediabetes and diabetes in NOD mice have been targeted with different outcomes by a variety of immunotherapies, including interferon (IFN)-γ. This cytokine may be instrumental in specific forms of tolerance by virtue of its ability to activate immunosuppressive tryptophan catabolism. Here, we provide evidence that IFN-γ fails to induce tolerizing properties in dendritic cells from highly susceptible female mice early in prediabetes. This effect is associated with impaired tryptophan catabolism, is related to transient blockade of the Stat1 pathway of intracellular signaling by IFN-γ, and is caused by peroxynitrite production. However, the use of a peroxynitrite inhibitor can rescue tryptophan catabolism and tolerance in those mice. This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan catabolism.
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影响因子：
30.5
作者：
Grohmann, U;Orabona, C;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
4.4
作者：
Grohmann, U;Bianchi, R;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
4.4
作者：
Deb, A;Haque, SJ;Williams, BRG
通讯作者：
Williams, BRG
DOI：
10.1073/pnas.96.16.9311
发表时间：
1999-08-03
影响因子：
11.1
作者：
Anderson, B;Park, BJ;Santamaria, P
通讯作者：
Santamaria, P
影响因子：
30.5
作者：
Kishimoto, H;Sprent, J
通讯作者：
Sprent, J