1 Introduction
Type 2 diabetes mellitus (T2DM) has become more common with the aging of the population and changing lifestyles, and in recent years, the worldwide incidence of T2DM has risen dramatically1. Many individuals with T2DM also have genetic variation, obesity, and decreased immune function, which increases the risk of infections, cardiovascular disorders, and cognitive disorders. These comorbidities are the main cause of death and disability in individuals with T2DM2,3. Firstly, genetics and environment are important factors in the high incidence of T2DM. According to a large cohort study, mutations in endocrine-related genes(such as Pax6, Hnf1Α, PDX1) affect the regulation of β cell development and insulin secretion and are more likely to develop T2DM. In addition, factors such as smoking and a high-energy diet are also common risks for T2DM4.
Overweight and obesity are positively associated with the risk of T2DM. In individuals with obesity, increased adipocytosis promotes the release of glycerol and free fatty acids as well as macrophage infiltration. Ongoing chronic inflammation stimulates T cell activation, which subsequently promotes the onset and development of insulin resistance (IR)5, and IR and pancreatic β cell dysfunction frequently work together to cause T2DM6. There is an important link between chronic inflammation, poor immune response, and insulin resistance. These findings have prompted researchers to delve deeper into possible interactions between insulin and T cells. However, researchers have examined the immune system in T2DM because it is an inflammatory illness. Many people with T2DM have abnormally high levels of T-cell reactivity, which correlates adversely with the C-peptide index7. Further, the pro-inflammatory cytokine interleukin (IL)-1β promotes β cell apoptosis when released in response to high glucose induction8, and tumor necrosis factor (TNF) has been found to exacerbate hyperglycemia in diabetic rats9. Further studies revealed that TNF-α activates c-Jun amino-terminal kinases (JNKs) and inhibitor of kappa B kinase beta(IKKβ)/nuclear factor kappa B (NF-κB) signaling10, contributing to the inactivation of insulin receptor-associated pathways. This leads to IR upregulates inhibitor of matrix metalloproteinases in keratinocytes, and inhibits wound healing during diabetes11. Therefore, T cell response plays an important role in promoting T2DM.
The influence of adaptive immunity on T2DM has gained increasing attention in recent years, and recent studies have indicated that the number of B -lymphocytes and CD8+ T cells are considerably higher in individuals with T2DM, whereas the numbers of total lymphocytes and CD4+T cells are decreased12. T2DM is characterized by an increase in inflammatory cytokines such as IFN-γ and IL-6 and a decrease in anti-inflammatory cytokines such as IL-1013. T2DM and its complications are caused in part by chronic inflammation owing to CD4+ T cell abnormalities. In this review, we discuss the role of different subpopulations of adaptive T cells in obesity and T2DM and explore the impact of T cell status on T2DM and the potential for immunotherapy.