Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression

Abstract

Nutritional deprivation suppresses immune function. The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight. Circulating levels of this adipocyte-derived hormone are proportional to fat mass but maybe lowered rapidly by fasting or increased by inflammatory mediators. The impaired T-cell immunity of mice now known to be defective in leptin (ob/ob) or its receptor (db/db), has never been explained. Impaired cell-mediated immunity and reduced levels of leptin are both features of low body weight in humans. Indeed, malnutrition predisposes to death from infectious diseases. We report here that leptin has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naive and memory T cells. Leptin increased Th1 and suppressed Th2 cytokine production. Administration of leptin to mice reversed the immunosuppressive effects of acute starvation. Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation.

Leptin in immuno-rheumatological diseases

“…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 …”

“…Leptin alone is unable to induce the proliferation and activation of mature human peripheral blood lymphocytes unless it is co-administered with other nonspecific immunostimulants, in which case leptin results in the induction of early (CD69) and late activation markers (CD25 and CD71) in both CD4 and CD8 lymphocytes. 16,44,55 Figure 1 Leptin functions in humans. Leptin, mainly secreted by white adipose tissue, travels through the blood, crossing the hematoencephalic barrier.…”

Effect of high-fat diet feeding on leptin receptor expression in white adipose tissue in rats: depot- and sex-related differential response

“…However, recent studies have suggested that leptin can play important physiological roles in an autocrine/paracrine way, acting in different types of cells such as adipocytes, hepatocytes, T-lymphocytes, pancreatic cells, etc. [9,10,24,28]. In fact, the role of leptin on white adipose tissue (WAT) has been reported to be essential in modulating the adipocytes' metabolic function [25], up-regulating fat oxidation [13] and decreasing lipogenesis [27].…”

Involvement of leptin signaling in the survival and maturation of bone marrow‐derived dendritic cells

“…In the recent years, accumulating evidence has established the role of leptin as a growth factor that modulates immune responses [2,3]. The structure of leptin has high similarity to members of the long-chain helical cytokines such as IL-6, IL-11, IL-12, G-CSF, leukemia inhibitory factor and oncostatin [4,5].…”

“…The structure of leptin has high similarity to members of the long-chain helical cytokines such as IL-6, IL-11, IL-12, G-CSF, leukemia inhibitory factor and oncostatin [4,5]. Several studies have revealed an important role for leptin in regulating lymphopoiesis and hematopoiesis [1,2,[6][7][8]. For example, leptin has been shown to stimulate proliferation and increase the production of a variety of cytokines in rodent T cells and monocytes/macrophages [2,[9][10][11].…”