Hou Weiping, Huang Gang, Cao Xuejiao, Zhang Yuanyuan, Zhang Jinbo, Li Yan
Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University Chongqing, Chongqing, China,
J Nephrol. 2014 Feb;27(1):19-28. doi: 10.1007/s40620-013-0020-5. Epub 2013 Dec 13.
Indoleamine 2, 3-dioxygenase (IDO), a heme-containing dioxygenase, can catalyze tryptophan degradation and produce a local microenvironment with tryptophan depletion and tryptophan metabolites accumulation, which may suppress T cell-mediated immunity and play an important immunosuppressive role in many diseases. Previous studies suggested that tryptophan depletion is an important immunosuppressive mechanism of IDO, while recent evidence shows that tryptophan metabolites may also be useful for inducing the T cell immune tolerance. However, it remains unclear whether tryptophan catabolites play a protective role in anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN), which is a type 1 T-helper (Th1)-mediated autoimmune disease.
We examined the effect of tryptophan catabolites, 3-hydroxykynurenine acid and 3-hydroxyanthranilic acid, on renal injury in experimental autoimmune glomerulonephritis (EAG) of Wistar-Kyoto rats and explored their protective mechanism.
Treatment by either 3-hydroxyanthranilic acid or 3-hydroxykynurenic acid attenuated the kidney disease of EAG rats, with decreased glomerular histological injury and inflammatory cell infiltration, lightened urinary protein, and improved renal function compared to phosphate buffered saline-treated EAG rats. This was associated with significantly increased apoptosis and decreased proliferation of splenic activated T cells in vivo, inducing the deviation of cytokines of antigen-special T cells from Th1 to Th2.
Tryptophan metabolites play an important immunosuppressive role in the development of anti-GBM GN and might offer a new strategy for treating this disease.
吲哚胺2,3-双加氧酶（IDO）是一种含血红素的双加氧酶，可催化色氨酸降解，产生色氨酸耗竭和色氨酸代谢产物积累的局部微环境，这可能抑制T细胞介导的免疫，并在许多疾病中发挥重要的免疫抑制作用。以往研究提示色氨酸耗竭是IDO的重要免疫抑制机制，而最近的证据表明色氨酸代谢产物也可能有助于诱导T细胞免疫耐受。然而，色氨酸分解代谢产物在抗肾小球基底膜（anti-GBM）肾小球肾炎（GN）（一种1型辅助性T细胞（Th1）介导的自身免疫性疾病）中是否发挥保护作用仍不清楚。
我们检测了色氨酸分解代谢产物3-羟基犬尿氨酸和3-羟基邻氨基苯甲酸对Wistar-Kyoto大鼠实验性自身免疫性肾小球肾炎（EAG）肾损伤的影响，并探讨了其保护机制。
与磷酸盐缓冲盐水处理的EAG大鼠相比，用3-羟基邻氨基苯甲酸或3-羟基犬尿氨酸治疗可减轻EAG大鼠的肾脏疾病，肾小球组织学损伤和炎性细胞浸润减少，尿蛋白减轻，肾功能改善。这与体内脾活化T细胞凋亡显著增加和增殖减少有关，诱导抗原特异性T细胞细胞因子从Th1向Th2偏移。
色氨酸代谢产物在anti-GBM GN的发生发展中起重要的免疫抑制作用，可能为治疗该疾病提供新策略。
