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犬尿氨酸途径——自身免疫内分泌疾病中先天免疫与适应性免疫的新联系。

The Kynurenine Pathway-New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies.

机构信息

Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, M. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.

出版信息

Int J Mol Sci. 2021 Sep 13;22(18):9879. doi: 10.3390/ijms22189879.

Abstract

The kynurenine pathway (KP) is highly regulated in the immune system, where it promotes immunosuppression in response to infection or inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the main enzyme of KP, has a broad spectrum of activity on immune cells regulation, controlling the balance between stimulation and suppression of the immune system at sites of local inflammation, relevant to a wide range of autoimmune and inflammatory diseases. Various autoimmune diseases, among them endocrinopathies, have been identified to date, but despite significant progress in their diagnosis and treatment, they are still associated with significant complications, morbidity, and mortality. The precise cellular and molecular mechanisms leading to the onset and development of autoimmune disease remain poorly clarified so far. In breaking of tolerance, the cells of the innate immunity provide a decisive microenvironment that regulates immune cells' differentiation, leading to activation of adaptive immunity. The current review provided a comprehensive presentation of the known role of IDO1 and KP activation in the regulation of the innate and adaptive arms of the immune system. Significant attention has been paid to the immunoregulatory role of IDO1 in the most prevalent, organ-specific autoimmune endocrinopathies-type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis.

摘要

犬尿氨酸途径 (KP) 在免疫系统中受到高度调节,它在感染或炎症时促进免疫抑制。吲哚胺 2,3-双加氧酶 1 (IDO1) 是 KP 的主要酶,对免疫细胞的调节具有广泛的活性,控制局部炎症部位免疫系统的刺激与抑制之间的平衡,与广泛的自身免疫和炎症性疾病相关。目前已经确定了各种自身免疫性疾病,其中包括内分泌疾病,但尽管在诊断和治疗方面取得了重大进展,但它们仍然与严重的并发症、发病率和死亡率有关。导致自身免疫性疾病发生和发展的确切细胞和分子机制迄今仍未得到充分阐明。在自身耐受的破坏中,先天免疫系统的细胞提供了一个决定性的微环境,调节免疫细胞的分化,导致适应性免疫的激活。本综述全面介绍了 IDO1 和 KP 激活在调节先天和适应性免疫系统中的已知作用。特别关注 IDO1 在最常见的、器官特异性自身免疫内分泌疾病-1 型糖尿病 (T1DM) 和自身免疫性甲状腺炎中的免疫调节作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e96a/8469440/275fb838100d/ijms-22-09879-g001.jpg

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