Decreased indoleamine 2,3-dioxygenase expression in dendritic cells and role of indoleamine 2,3-dioxygenase-expressing dendritic cells in immune thrombocytopenia
Decreased indoleamine 2,3-dioxygenase expression in dendritic cells and role of indoleamine 2,3-dioxygenase-expressing dendritic cells in immune thrombocytopenia
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树突状细胞中吲哚胺 2,3-双加氧酶表达减少以及表达吲哚胺 2,3-双加氧酶的树突状细胞在免疫性血小板减少症中的作用
DOI：
10.1007/s00277-012-1451-0
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发表时间：
2012-10-01
影响因子：
3.5
通讯作者：
Hou, Ming
中科院分区：
文献类型：
--
作者：
Xu, Shu-qian;Wang, Chun-yan;Hou, Ming
树突状细胞（DCs）中吲哚胺2，3-双加氧酶（IDO）的表达可诱导或维持外周免疫耐受。在自身免疫性疾病中观察到IDO介导的色氨酸催化酶受损。为了探讨IDO介导的色氨酸催化剂和IDO表达的DC在免疫性血小板减少症中的作用，采用高压液相色谱法检测犬尿氨酸的浓度。流式细胞术和western blot分析IDO的表达。流式细胞术检测CTLA-4-IG刺激IDO（+）DC对T细胞增殖、活化、淋巴细胞凋亡及T淋巴细胞增殖的影响。我们发现免疫性血小板减少症（ITP）患者DC中IDO的表达显著降低。CTLA-4-IG可显著增加ITP患者DC中功能性IDO的表达。CTLA-4-IG刺激IDO（+）DCs后，可抑制T细胞增殖和活化，促进淋巴细胞凋亡，增加T淋巴细胞百分率。这些结果表明，IDO在DC中的表达降低可能在ITP中起关键作用。CTLA-4-IG可明显改善ITP患者IDO表达的紊乱。用CTLA-4-IG刺激的IDO（+）DC通过IDO依赖性机制抑制免疫反应。提高IDO在DCs中的表达和活性可能是治疗ITP的一种有前景的方法。
Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) can induce or maintain peripheral immune tolerance. Impaired IDO-mediated tryptophan catabolism has been observed in autoimmune diseases. In order to investigate the effects of IDO-mediated tryptophan catabolism and IDO-expressing DCs in immune thrombocytopenia, the concentrations of kynurenine were detected by high-pressure liquid chromatography. The expressions of IDO were analyzed by flow cytometry and western blot analysis. The effects of IDO(+) DCs stimulated with CTLA-4-Ig on T cells proliferation and activation, lymphocyte apoptosis, and Tregs were measured by flow cytometry. We found that the expression of IDO in DCs of immune thrombocytopenia (ITP) patients was significantly decreased. CTLA-4-Ig significantly increased the expression of functional IDO in DCs of ITP patients. IDO(+) DCs stimulated with CTLA-4-Ig suppressed T cells proliferation and activation, promoted lymphocyte apoptosis, and increased the percentage of Tregs. These results suggest that decreased IDO expression in DCs may play a critical role in ITP. CTLA-4-Ig successfully corrected the disorder of IDO expression in ITP. IDO(+) DCs stimulated with CTLA-4-Ig inhibited immune responses by an IDO-dependent mechanism. Increasing the expression and activity of IDO in DCs might be a promising therapeutic approach for ITP.