Role of Leptin in the Activation of Immune Cells

Abstract

Adipose tissue is an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that may be present in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response, innate and adaptive response, both in normal and pathological conditions. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response.

Leptin in immuno-rheumatological diseases

“…In vitro neutralization with a leptin monoclonal antibody during stimulation with anti-CD3 and anti-CD28 antibodies resulted in Treg proliferation, which was IL-2 dependent. 36,58 These findings indicate that leptin signaling is clearly involved in maintaining the anergic state of human Tregs. In agreement with this, both leptindeficient (ob/ob mice) and leptin receptor-deficient mice (db/db mice) were associated with a marked increase in the number of Tregs (Figure 3).…”

“…The primary amino acid sequence of leptin indicated that it could belong to the long-chain helical cytokine family, 36,42 with members such as IL-2 and IL-12. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune response.…”

“…In fact, a main aspect of the effects of leptin on the immune system is its action as a proinflammatory cytokine. The full length functional leptin receptor isoform OB-Rb shows sequence homology to members of class I cytokine receptor (gp130) superfamily, 30,36 which includes the receptor for IL-6, leucocyte inhibitory factor and granulocyte colony-stimulating factor. This receptor lacks intrinsic tyrosine kinase activity, is involved in several downstream signal transduction pathways, and has been identified in immune cells of both animals and humans.…”

“…43,44 OB-Rb has been shown to have the signaling capabilities of IL-6-type cytokine receptors, activating janus kinases and signal transducers and activators of transcription (STAT), phosphatidylinositol 3-kinase and the mitogen-activated protein kinase (MAPK) signaling pathways. 36,41,45 Like other cytokine receptor family members, OB-Rb is internalized upon ligand binding via …”

“…Modulation of the immune system by leptin is exerted at the development, proliferation, antiapoptotic, maturation and activation levels. 24,36 In fact, leptin receptors can also be found in different tissues and immune cell types, including various subpopulations of T and B lymphocytes, dendritic cells, monocytes, neutrophils, macrophages and natural killer (NK) cells. 18,[37][38][39][40][41] The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune responses.…”