Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Buck Institute for Research in Aging, Novato, CA, United States.
Front Endocrinol (Lausanne). 2023 Mar 13;14:1128622. doi: 10.3389/fendo.2023.1128622. eCollection 2023.
The signaling pathways downstream of the insulin receptor (InsR) are some of the most evolutionarily conserved pathways that regulate organism longevity and metabolism. InsR signaling is well characterized in metabolic tissues, such as liver, muscle, and fat, actively orchestrating cellular processes, including growth, survival, and nutrient metabolism. However, cells of the immune system also express the InsR and downstream signaling machinery, and there is increasing appreciation for the involvement of InsR signaling in shaping the immune response. Here, we summarize current understanding of InsR signaling pathways in different immune cell subsets and their impact on cellular metabolism, differentiation, and effector versus regulatory function. We also discuss mechanistic links between altered InsR signaling and immune dysfunction in various disease settings and conditions, with a focus on age related conditions, such as type 2 diabetes, cancer and infection vulnerability.
胰岛素受体 (InsR) 下游的信号通路是调节生物寿命和代谢的最具进化保守性的通路之一。InsR 信号在代谢组织中得到了很好的描述，如肝脏、肌肉和脂肪，积极协调细胞过程，包括生长、存活和营养代谢。然而，免疫系统的细胞也表达 InsR 和下游信号机制，并且越来越认识到 InsR 信号在塑造免疫反应中的作用。在这里，我们总结了不同免疫细胞亚群中 InsR 信号通路的最新理解及其对细胞代谢、分化以及效应器与调节功能的影响。我们还讨论了改变的 InsR 信号与各种疾病状态和条件下的免疫功能障碍之间的机制联系，重点关注与年龄相关的疾病，如 2 型糖尿病、癌症和易感染性。
