Leptin Regulation of Immune Responses

Leptin is a regulatory hormone with multiple roles in the immune system. We favor the concept that leptin signaling ‘licenses’ various immune cells to engage in immune responses and/or to differentiate. Leptin is an inflammatory molecule that is capable of activating both adaptive and innate immunity. It can also ‘enhance’ immune functions, including inflammatory cytokine production in macrophages, granulocyte chemotaxis, and increased Th17 proliferation. Leptin can also ‘inhibit’ cells; CD4+ T cells are inhibited from differentiating into regulatory T cells in the presence of elevated leptin, while NK cells can exhibit impaired cytotoxicity under the same circumstances. Consequently, understanding the effect of leptin signaling is important to appreciate various aspects of immune dysregulation observed in malnutrition, obesity, and autoimmunity.

TrendsLeptin signaling can regulate innate inflammatory responses, such as cytokine production in macrophages and mast cells, as well as leptin-mediated chemotaxis in granulocytes.Leptin signaling can regulate adaptive immunity. It is required for Th17 differentiation through upregulation of transcription of RORγt.Leptin signaling can suppress regulatory T cell (Treg) differentiation.Inhibition of the leptin receptor blocks macrophage microbicidal and phagocytic functions, as well as the maturation of dendritic cells.Leptin can inhibit natural killer (NK) cell activation under certain circumstances, a unique effect not observed in other cell types.