The Arthur Riggs Diabetes & Metabolism Research Institute at the Beckman Research Institute.
Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA.
Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):397-403. doi: 10.1097/MED.0000000000000646.
Type 1 diabetes (T1D) results from the loss of immune tolerance to pancreatic beta-cells leading to their destruction. Immune intervention therapies tested in T1D so far delayed progression but failed to restore tolerance, which partly explains their lack of durable clinical efficacy.
The role of beta-cells and islets themselves in dialogue with their micro- and macro-environment including the immune system and the intestinal microbiome is increasingly evident. Indeed, islets can both maintain and break immune tolerance. Some recent immune therapies in cancer that block immune regulation also break tolerance. Induction of immune tolerance requires activating immune activation too, whereas immune suppression precludes this process. Immunotherapy alone my not suffice without engaging islets to restore tolerance and preserve beta-cell function.
New insight into the role of islet tissue and its interaction with its environment in preserving or breaking tolerance has contributed to understand the development of islet autoimmunity and T1D. Knowing which factors in islets and the immune system contribute to maintaining, breaking, and restoring the balance in the immune system is critical to prevent initiation and reverse disease progression, and guides the design of novel tolerogenic strategies for durable therapeutic intervention and remission that target both the immune system and distressed islets.
1 型糖尿病（T1D）是由于对胰腺β细胞的免疫耐受丧失导致其破坏而引起的。迄今为止，在 T1D 中测试的免疫干预疗法虽然延缓了疾病进展，但未能恢复耐受性，这在一定程度上解释了它们缺乏持久临床疗效的原因。
β细胞和胰岛本身与其微环境和宏环境（包括免疫系统和肠道微生物组）之间的对话作用越来越明显。事实上，胰岛既能维持又能打破免疫耐受。一些最近在癌症中阻断免疫调节的免疫疗法也会打破耐受。诱导免疫耐受需要激活免疫激活，而免疫抑制则阻止了这一过程。如果不与胰岛结合来恢复耐受性并保留β细胞功能，单独的免疫疗法可能不足以发挥作用。
对胰岛组织及其与环境相互作用在维持或打破耐受中的作用的新认识有助于理解胰岛自身免疫和 T1D 的发展。了解胰岛和免疫系统中的哪些因素有助于维持、打破和恢复免疫系统的平衡对于预防疾病的发生和逆转疾病的进展至关重要，并为针对免疫系统和受损胰岛的持久治疗干预和缓解的新型耐受策略的设计提供了指导。
