Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes.
Host-microbiota interactions shaping T-cell response and tolerance in type 1 diabetes.
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DOI：
10.3389/fimmu.2022.974178
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
1型糖尿病（T1 D）是一种复杂的多基因自身免疫性疾病，涉及T细胞驱动的β细胞破坏，导致高血糖症。T1 D无法治愈，患者依赖外源性胰岛素治疗疾病。T1 D与特定的疾病易感等位基因相关。然而，疾病发展的易感性并不仅仅是由它们预测的。这是最好的例子，观察到一个同卵双胞胎只有35%的机会发展T1 D后，他们的双胞胎的诊断。这为环境触发因素在T1 D发病率中发挥重要作用提供了强有力的理由。多项研究表明，肠道微生物群和改变其组成的环境因素可能会加剧或防止T1 D发作。在这篇综述中，我们讨论了最近的文献突出与T1 D相关的微生物物种。我们探讨了机制研究，提出了这些微生物物种如何调节T1 D的适应性免疫反应，重点是T细胞反应。我们涵盖的主题范围从肠-胸腺和肠-胰腺通信，外周耐受性的微生物调节，胰岛抗原的微生物肽的分子模拟。在新生儿胸腺细胞发育的影响，在不断积累的证据，我们还推测分子模拟和胸腺选择的背景下，T1 D发病机制之间的联系。最后，我们将探讨这些观察结果如何为这种疾病的未来治疗方法提供信息。
Type-1 Diabetes (T1D) is a complex polygenic autoimmune disorder involving T-cell driven beta-cell destruction leading to hyperglycemia. There is no cure for T1D and patients rely on exogenous insulin administration for disease management. T1D is associated with specific disease susceptible alleles. However, the predisposition to disease development is not solely predicted by them. This is best exemplified by the observation that a monozygotic twin has just a 35% chance of developing T1D after their twin’s diagnosis. This makes a strong case for environmental triggers playing an important role in T1D incidence. Multiple studies indicate that commensal gut microbiota and environmental factors that alter their composition might exacerbate or protect against T1D onset. In this review, we discuss recent literature highlighting microbial species associated with T1D. We explore mechanistic studies which propose how some of these microbial species can modulate adaptive immune responses in T1D, with an emphasis on T-cell responses. We cover topics ranging from gut-thymus and gut-pancreas communication, microbial regulation of peripheral tolerance, to molecular mimicry of islet antigens by microbial peptides. In light of the accumulating evidence on commensal influences in neonatal thymocyte development, we also speculate on the link between molecular mimicry and thymic selection in the context of T1D pathogenesis. Finally, we explore how these observations could inform future therapeutic approaches in this disease.
影响因子：
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作者：
Espinoza-Jiménez A;Rivera-Montoya I;Cárdenas-Arreola R;Morán L;Terrazas LI
通讯作者：
Terrazas LI