Regulation of the immune system by the insulin receptor in health and disease.

Priya Makhijani, Paulo José Basso, Yi Tao Chan, Nan Chen, Jordan Baechle, Saad Khan, David Furman, Sue Tsai, Daniel A Winer

Journal: Frontiers in endocrinology 2023;14():1128622

PMID: 36992811

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Abstract

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.

Address: Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.; Buck Institute for Research in Aging, Novato, CA, United States.; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.; Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.; Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.; Buck Artificial Intelligence Platform, Buck Institute for Research on Aging, Novato, CA, United States.; Stanford 1, 000 Immunomes Project, Stanford School of Medicine, Stanford University, Stanford, CA, United States.; Instituto de Investigaciones en Medicina Traslacional (IIMT), Universidad Austral, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Pilar, Argentina.; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, United States.

DOI: 10.3389/fendo.2023.1128622

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MeSH Terms: Humans, Receptor, Insulin, Insulin, Diabetes Mellitus, Type 2, Signal Transduction, Immune System