Leptin in metabolic-immune crosstalk: Mechanisms of T cell regulation and implications for autoimmune disease therapy

Leptin, a multifunctional hormone primarily secreted by adipose tissue, plays a crucial role in regulating body weight, appetite, energy expenditure, and metabolic processes. Beyond regulating metabolic pathways, leptin demonstrates notable immunoregulatory capabilities. It modulates a wide range of biological functions, including glycemic control, hematopoietic processes, and bone metabolism. The discovery of leptin has significantly advanced our understanding of the crosstalk between metabolic homeostasis and immune system functionality. Recent research highlights its critical role in immune responses, particularly in modulating T lymphocytes. This hormone transmits nutritional signals to the immune system, promoting pro-inflammatory Th1 and Th17 responses while inhibiting anti-inflammatory Treg cell proliferation. Consequently, it is a pivotal regulator integrating metabolic signals to control the balance between inflammation and immune tolerance. In this review, we will synthesize the latest advancements in leptin research, leptin receptor signaling, the hormone's impact on T cells and immune responses, as well as its potential pathogenic roles in autoimmune diseases, including Systemic Lupus Erythematosus (SLE), psoriasis, vitiligo, and other autoimmune disorders. Our objective is to provide a comprehensive analysis of leptin's properties and its unique roles in autoimmune conditions, with the aim of providing new insights into effective and holistic therapeutic strategies.