Regulation, Communication, and Functional Roles of Adipose Tissue-Resident CD4⁺ T Cells in the Control of Metabolic Homeostasis

Evidence accumulated over the past few years has documented a critical role for adipose tissue (AT)-resident immune cells in the regulation of local and systemic metabolic homeostasis. In the lean state, visceral adipose tissue (VAT) is predominated by anti-inflammatory T-helper 2 (Th2) and regulatory T (Treg) cell subsets. As obesity progresses, the population of Th2 and Treg cells decreases while that of the T-helper 1 (Th1) and T-helper 17 (Th17) cells increases, leading to augmented inflammation and insulin resistance. Notably, recent studies also suggest a potential role of CD4⁺ T cells in the control of thermogenesis and energy homeostasis. In this review, we have summarized recent advances in understanding the characteristics and functional roles of AT CD4⁺ T cell subsets during obesity and energy expenditure. We have also discussed new findings on the crosstalk between CD4⁺ T cells and local antigen-presenting cells (APCs) including adipocytes, macrophages, and dendritic cells (DCs) to regulate AT function and metabolic homeostasis. Finally, we have highlighted the therapeutic potential of targeting CD4⁺ T cells as an effective strategy for the treatment of obesity and its associated metabolic diseases.