Role Of Leptin In Immune Cell Development And Innate Immunity

Leptin is an adipokine with structural and signaling similarity to the helical cytokines and therefore plays an essential role in the modulation of hematopoiesis and innate immune cells. Obese individuals or mice are characterized by leptin resistance, on the contrary; conditions such as starvation and malnutrition are characterized by decreased leptin. Both of these conditions create a defective immune system and increased susceptibility to infection. The leptin-deficient ob/ob mouse and the mouse lacking functional leptin receptor, the db/db mouse, are used as effective models to study these effects of leptin on the immune system. There is thymic atrophy and a decrease in the bone marrow cell population in the ob/ob mouse. All circulating and tissue-resident innate immune cells such as the monocytes, macrophages, neutrophils, dendritic cells and natural killer cells express the leptin receptor and are able to respond to leptin and transduce leptin signal. Indeed, obesity or lack of leptin disrupts signaling though the leptin receptor and its downstream JAK/STAT pathway. Leptin is either essential or enhances the functional capability of innate immune cells. It induces innate immune cells to produce pro-inflammatory cytokines and promotes phagocytosis, chemotaxis, cytotoxicity and effective antigen presentation, in both in vivo and in vitro conditions. The decreased functional capacity of the innate immune cells in the absence of leptin could account for the increased susceptibility to infection in the obese and malnourished. This review discusses the various roles of leptin in hematopoiesis and its ability to modify the functional capacity of innate immune cells and their development in the marrow.