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

Lam, Queenie Lai Kwan; Liu, Shuxun; Cao, Xuetao; Lu, Liwei

doi:10.1002/eji.200636602

Cited by 95 publications

(98 citation statements)

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“…Leptin activates NF-kB in dendritic cells, whereas a leptinsignaling deficiency leads to enhanced levels of the inhibitor protein of NF-kB ( Figure 2). 37 The above-described role of leptin in the function of the immune system could be relevant in both cellular and humoral immunity.…”

Section: Leptin and Autoimmunity M Vadacca Et Al 204mentioning

confidence: 99%

“…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. This concept is discussed in detail in the present review.…”

Section: Introductionmentioning

confidence: 99%

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Leptin in immuno-rheumatological diseases

et al. 2011

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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. Since its discovery in 1994, leptin has attracted increasing interest in the scientific community for its pleiotropic actions. One of these functions is the relationship between nutritional status and immune competence. It structurally resembles proinflammatory cytokines, such as IL-6 and IL-12. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune responses. The role of leptin in regulating immune responses has been assessed in vitro as well as in clinical studies. It has been shown that disease conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders, such as autoimmune diseases, are associated with the increased secretion of leptin and the production of proinflammatory pathogenic cytokines. In this paper, we review the most recent advances of the role of leptin in immune-rheumatological diseases, and we discuss whether strategies aimed at modifying leptin levels could represent innovative and therapeutic tools for autoimmune disorders. Keywords: adipokines; autoimmune diseases; leptin; rheumatic diseases INTRODUCTIONThe existence of a factor secreted by white adipose tissue (WAT), which acts to control feeding, weight and WAT mass, was first proposed by Kennedy 1 and is supported by monogenic mutations resulting in obesity. [2][3][4] WAT is composed of adipocytes filled mainly with triacylglycerol and embedded in loose connective tissue containing adipocyte precursors, fibroblasts, immune and other cells. Obesity, the condition that originally motivated the research on WAT, is characterized by low-grade systemic inflammation. It is thought that excess WAT can contribute to the maintenance of obesity through inflammation-inducing lipotoxicity by secreting factors that stimulate the synthesis of inflammatory agents in other organs and by secreting inflammatory agents itself. 5 The current view of WAT states that it is an active contributor to body homeostasis by sending out and responding to signals that modulate appetite, energy expenditure, insulin sensitivity, the endocrine and reproductive systems, bone metabolism, inflammation and immunity. 6 Several findings have converged to indicate that adipocytes share certain properties with immune cells, such as complement activation 7 and proinflammatory cytokine production. 8 Fat cell precursors also share features with macrophages. Numerous genes that code for transcription factors, cytokines, inflammatory signaling molecules, and fatty acid transporters are essential for adipocyte biology and are also expressed and functional in macrophages. 9 Adipose tissue secrets a variety of factors: the term 'adipokine' is generally given to any protein that can be synthesized and secreted by adipocytes. Among these factors, only leptin and adiponectin (and possibly resistin, adipsi...

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Section: Leptin and Autoimmunity M Vadacca Et Al 204mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Leptin in immuno-rheumatological diseases

et al. 2011

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“…This report demonstrated that human DC express functional leptin receptors and that leptin promotes differentiation of peripheral bloodderived DC, protects them from apoptosis, modulates cytokine production, and -quite importantly -licenses them for Th1 priming of CD4 + T cells [13]. In this issue of the European Journal of Immunology, Lam et al [14] describe for the first time the effect of leptin receptor deficiency on DC survival, maturation and function in mice. This report by Lam et al [14]describes how murine bone marrow-derived DC express functional leptin receptors and respond to leptin stimulation with activation of the JAK2 pathway.…”

mentioning

confidence: 95%

“…Despite the fact that Mattioli et al [13] and Lam et al [14] evaluated the effect of leptin in DC using two different organisms (human and mouse respectively) and from two opposite experimental perspectives (the addition of leptin in the study by Mattioli et al [13], leptin receptor-deficiency/blockade in Lam et al [14]), the pattern of the findings is astoundingly similar: in both systems, leptin protects DC from apoptosis, induces DC maturation, upregulates production of TNF-a and IL-12 while downregulating IL-10 synthesis, and increases the ability of DC to stimulate CD4 + lymphocytes. The only major difference observed between the two reports concerns the effect of leptin on the expression of co-stimulatory molecules by DC, an effect which was present in the report by Lam et al [14] but absent in that of Mattioli et al [13].…”

mentioning

confidence: 98%

“…In this issue of the European Journal of Immunology, Lam et al [14] describe for the first time the effect of leptin receptor deficiency on DC survival, maturation and function in mice. This report by Lam et al [14]describes how murine bone marrow-derived DC express functional leptin receptors and respond to leptin stimulation with activation of the JAK2 pathway. When the investigators attempted to generate DC from the bone marrow of db/db leptin receptor-deficient mice, they obtained a significantly lower yield compared with cells derived from their WT counterparts, even after stimulation and induction of maturation with LPS.…”

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confidence: 99%

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Leptin: Nourishment for the immune system

Fantuzzi

2006

Eur J Immunol

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Leptin, a protein produced by adipocytes, exerts several functions, including modulation of the immune response. A report in this issue of the European Journal of Immunology describes for the first time the effect of either leptin receptor deficiency or blockade on murine dendritic cell (DC) maturation, survival and function. The study describes how leptin receptor deficiency/blockade delays DC maturation and promotes apoptosis, shifts the balance between pro-and anti-inflammatory cytokine production, and reduces the ability of DC to stimulate CD4 + lymphocytes. These exciting novel data add an important piece of evidence to the picture of the role of leptin in immunity and inflammation and generate the possibility that many of the effects of leptin on T lymphocytes might be mediated through DC. Leptin, a protein produced by adipocytes and released into the systemic circulation, acts as a master hormone, controlling most of the body's functions involved in energy acquisition and utilization. Although leptin is best known for its role in regulating food intake, this adipokine controls several other critical systems, including modulation of various endocrine axes, bone metabolism, as well as the immune/inflammatory response [1].The observation that an absence of leptin or its receptor results in alterations of the cellularity and function of the immune system was made several years before the term leptin had been coined and the genes for leptin and its receptor identified. In fact, the finding of thymic atrophy and reduced lymphocyte function in ob/ob (leptin-deficient) and db/db (leptin receptordeficient) mice dates to the late 1970s and early 1980s [2][3][4][5]. Cloning of leptin in 1994 and the subsequent rapid identification of its receptor lead to a renewed interest and reevaluation of those discoveries of the late 1970s/early 1980s. In agreement with the early observations of lymphocyte abnormalities in ob/ob and db/db mice, most of the studies on the role of leptin in regulating immune responses focused on the effect of this adipokine on the lymphoid compartment, particularly maturation, function and survival of T lymphocytes. A critical finding of the majority of these studies was the demonstration that leptin skews the immune response towards a Th1 phenotype and protects T lymphocytes from apoptosis [6,7], possibly accounting for the protective effect of leptin-and leptin receptor-deficiency in models of autoimmune/inflammatory conditions [8][9][10]. Studies on the role of leptin in the modulation of monocytes/macrophages, neutrophils, basophils, eosinophils and natural killer cells soon followed (see [11,12] for reviews).However, it was not until 2005 that the first report on the effect of leptin on dendritic cells (DC) was published

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Natural killer cell degeneration exacerbates experimental arthritis in mice via enhanced interleukin‐17 production

Lo¹,

Lam²,

Sun³

et al. 2008

Arthritis & Rheumatism

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Objective. An altered phenotype and dysfunction of natural killer (NK) cells have been observed in patients with rheumatoid arthritis. The aim of this study was to determine whether dysregulated NK cells contribute to the pathogenesis of experimental arthritis.Methods Conclusion. These results suggest that NK cells play a protective role in the development of experimental arthritis, an effect that is possibly mediated by suppressing Th17 cell generation via IFN␥ production.

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

Cited by 95 publications

References 49 publications

Leptin in immuno-rheumatological diseases

Leptin in immuno-rheumatological diseases

Leptin: Nourishment for the immune system

Natural killer cell degeneration exacerbates experimental arthritis in mice via enhanced interleukin‐17 production

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