Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
BC Children's Hospital Research Institute, Vancouver, BC, Canada.
Diabetologia. 2021 Nov;64(11):2378-2388. doi: 10.1007/s00125-021-05565-6. Epub 2021 Sep 22.
Type 1 diabetes results from defects in immune self-tolerance that lead to inflammatory infiltrate in pancreatic islets, beta cell dysfunction and T cell-mediated killing of beta cells. Although therapies that broadly inhibit immunity show promise to mitigate autoinflammatory damage caused by effector T cells, these are unlikely to permanently reset tolerance or promote regeneration of the already diminished pool of beta cells. An emerging concept is that certain populations of immune cells may have the capacity to both promote tolerance and support the restoration of beta cells by supporting proliferation, differentiation and/or regeneration. Here we will highlight three immune cell types-macrophages, regulatory T cells and innate lymphoid cells-for which there is evidence of dual roles of immune regulation and tissue regeneration. We explore how findings in this area from other fields might be extrapolated to type 1 diabetes and highlight recent discoveries in the context of type 1 diabetes. We also discuss technological advances that are supporting this area of research and contextualise new therapeutic avenues to consider for type 1 diabetes.
1 型糖尿病是由于免疫自身耐受缺陷导致胰岛炎症浸润、β细胞功能障碍和 T 细胞介导的β细胞杀伤所致。虽然广泛抑制免疫的疗法有希望减轻效应 T 细胞引起的自身炎症损伤，但这些疗法不太可能永久重置耐受或促进已经减少的β细胞池的再生。一个新出现的概念是，某些免疫细胞群体可能具有促进耐受和通过支持增殖、分化和/或再生来支持β细胞恢复的能力。在这里，我们将重点介绍三种免疫细胞类型——巨噬细胞、调节性 T 细胞和先天淋巴细胞，它们具有免疫调节和组织再生的双重作用的证据。我们探讨了这一领域的其他领域的发现如何可以推断到 1 型糖尿病，并强调了 1 型糖尿病背景下的最新发现。我们还讨论了支持这一研究领域的技术进步，并将新的治疗途径置于考虑之中。
