A Key Role of Leptin in the Control of Regulatory T Cell Proliferation

Rosa, Veronica De; Procaccini, Claudio; Calı̀, Gaetano; Pirozzi, Giuseppe; Fontana, Silvia; Zappacosta, Serafino; Cava, Antonio La; Matarese, Giuseppe

doi:10.1016/j.immuni.2007.01.011

Cited by 564 publications

(565 citation statements)

References 48 publications

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“…Moreover, leptin-deficient low-density lipoprotein receptor-knockout (ldlr -) mice showed enhanced Foxp3 expression and reduced atherosclerotic lesion formation (35). The mechanism by which leptin negatively affects regulatory T cells has not been determined, although our results, showing increased numbers of regulatory T cells in MRL/Mp-Fas lpr -ob/ob mice, are consistent with previous findings (36).…”

Section: Discussionsupporting

confidence: 91%

Deficient Leptin Signaling Ameliorates Systemic Lupus Erythematosus Lesions in MRL/Mp-Faslpr Mice

Fujita

Fujii

Mimori

et al. 2014

The Journal of Immunology

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Leptin is secreted by adipocytes, the placenta, and the stomach. It not only controls appetite through leptin receptors in the hypothalamus, it also regulates immunity. In the current study, we produced leptin-deficient MRL/Mp-Faslpr mice to investigate the potential role of leptin in autoimmunity. C57BL/6J-ob/ob mice were backcrossed with MRL/Mp-Faslpr mice, which develop human systemic lupus erythematosus (SLE)-like lesions. The effects of leptin deficiency on various SLE-like manifestations were investigated in MRL/Mp-Faslpr mice. The regulatory T cell population in the spleen was analyzed by flow cytometry, and the effects of leptin on regulatory T cells and Th17 cells were evaluated in vitro. Compared with leptin-producing MRL/Mp-Faslpr mice, leptin-deficient MRL/Mp-Faslpr mice showed less marked splenomegaly and a particularly low population of CD3+CD4−CD8−B220+ T cells (lpr cells). Their serum concentrations of Abs to dsDNA were lower, and renal histological changes at age 20 wk were ameliorated. Regulatory T cells were increased in the spleens of leptin-deficient MRL/Mp-Faslpr mice. Leptin suppressed regulatory T cells and enhanced Th17 cells in vitro. In conclusion, blockade of leptin signaling may be of therapeutic benefit in patients with SLE and other autoimmune diseases.

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Section: Discussionsupporting

confidence: 91%

Deficient Leptin Signaling Ameliorates Systemic Lupus Erythematosus Lesions in MRL/Mp-Faslpr Mice

Fujita

Fujii

Mimori

et al. 2014

The Journal of Immunology

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“…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).…”

Section: Leptin and Autoimmunity M Vadacca Et Al 205mentioning

confidence: 78%

“…5 Further effects of leptin in immunity involves the suppression of CD4 1 CD25 1 regulatory T-cell (Treg) proliferation. 5,58 It has been recently shown that freshly isolated Tregs produce leptin. Moreover, the leptin receptor is highly expressed on the cell surface of Tregs.…”

Section: Leptin and Autoimmunity M Vadacca Et Al 205mentioning

confidence: 99%

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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“…For instance, soil‐transmitted helminths (STHs) can regulate systemic inflammation via a response dominated by anti‐inflammatory cytokines such as IL‐10, regulating the concentration of the inflammatory cytokines secreted by adipose tissue such as TNF‐α, IL‐6 and leptin 9, 10, 11. In addition to its role in inflammation processes, leptin is a hormone with other roles in human metabolism such as regulation of energy intake/expenditure, hematopoiesis and gut permeability 12, 13, 14, 15…”

Section: Introductionmentioning

confidence: 99%

Intestinal parasites: Associations with intestinal and systemic inflammation

Zavala

García

Camacho

et al. 2018

Parasite Immunology

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SummaryThe aim of the present study was to evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school‐aged children with high rates of obesity. Plasma concentrations of C‐Reactive Protein (CRP), leptin, TNF‐α, IL‐6 and IL‐10 were measured as systemic inflammation markers and count of stool leukocytes as marker of intestinal inflammation in 291 children (6‐10 years). Intestinal parasitic infection was measured by stool examination. Logistic regression analyses were performed to determine the odds of having high inflammatory markers for each parasite or group of parasites as compared to parasite‐free children while adjusting for sex, age, mother's educational level and percentage of body fat. The prevalence of soil‐transmitted helminths and intestinal protozoa infections was 12% and 36%, respectively. Parasitic infection was not associated with CRP, IL‐6, IL‐10 or TNF‐α. Children infected with Ascaris lumbricoides (aOR: 5.91, 95% CI: 1.97‐17.70) and Entamoeba coli (aOR: 8.46, 95% CI: 2.85‐25.14) were more likely to have higher stool leucocytes than parasite‐free children. Children with multiple infections (aOR: 10.60, 95% CI: 2.85‐25.14) were more likely to have higher leptin concentrations than parasite‐free children. Intestinal parasitic infection was not associated with systemic inflammation, but was associated with intestinal inflammation. Having multiple infections were associated with higher leptin concentrations.

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A Key Role of Leptin in the Control of Regulatory T Cell Proliferation

Cited by 564 publications

References 48 publications

Deficient Leptin Signaling Ameliorates Systemic Lupus Erythematosus Lesions in MRL/Mp-Faslpr Mice

Deficient Leptin Signaling Ameliorates Systemic Lupus Erythematosus Lesions in MRL/Mp-Faslpr Mice

Leptin in immuno-rheumatological diseases

Intestinal parasites: Associations with intestinal and systemic inflammation

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