Spleen Hemolytic Plaque-Forming Cell Response and Generation of Cytotoxic Cells in Genetically Obese (C57B1/6J &lt;i&gt;ob&lt;/i&gt;/&lt;i&gt;ob&lt;/i&gt;) Mice

Chandra, Ranjit Kumar; Au, B.

doi:10.1159/000232498

Cited by 34 publications

(23 citation statements)

References 11 publications

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“…mice, suggesting that supraphysiologic amounts of leptin may influence lymphocyte cellularity in the thymus. In addition, as previously demonstrated (15)(16)(17)(18)(19), spleen weight was significantly reduced in ob͞ob mice compared with ϩ͞? mice, and leptin-replacement normalized spleen weight (spleen weight was 40.00 Ϯ 8.52, 65.00 Ϯ 2.89, and 63.70 Ϯ 3.75 mg in ob͞ob, leptin-replaced ob͞ob, and ϩ͞?…”

Section: Effect Of Exogenous Leptin On Leukocyte Populations In Ob͞obsupporting

confidence: 78%

“…mice) (16)(17)(18)(19). In particular, CD4 ϩ CD8 ϩ were reduced by 59%, CD4 ϩ CD8 Ϫ by 54%, CD4 Ϫ CD8 ϩ by 36%, and CD4 Ϫ CD8 Ϫ by 31% in ob͞ob mice compared with ϩ͞?…”

Section: Effect Of Exogenous Leptin On Leukocyte Populations In Ob͞obmentioning

confidence: 97%

“…Hyperresponsiveness to monocyte͞macrophage-activating stimuli, i.e., endotoxin [lipopolysaccharide (LPS)] or tumor necrosis factor (TNF) ␣, is present in leptin-deficient (ob͞ob) mice (9)(10)(11). Additionally, decreased circulating leptin levels are associated with reduced lymphocyte cellularity in the thymus and spleen (15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

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Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: Role of tumor necrosis factor α and IL-18

Faggioni

Jones-Carson

Reed

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

310

225

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The role of leptin was investigated in two models of T cell-mediated hepatitis: the administration of Con A or of Pseudomonas aeruginosa exotoxin A (PEA). In both models, leptin-deficient (ob͞ob) mice were protected from liver damage and showed lower induction of tumor necrosis factor (TNF) ␣ and IL-18 compared with their lean littermates. Neutralization of TNF-␣ reduced induction of IL-18 by either Con A (70% reduction) or PEA (40% reduction). Pretreatment of lean mice with either soluble TNF receptors or with an anti-IL-18 antiserum significantly reduced Con A-and PEA-induced liver damage. The simultaneous neutralization of TNF-␣ and IL-18 fully protected the mice against liver toxicity. However, neutralization of either IL-18 or TNF-␣ did not inhibit Con A-induced production of IFN-␥. Thymus atrophy and alterations in the number of circulating lymphocytes and monocytes were observed in ob͞ob mice. Exogenous leptin replacement restored the responsiveness of ob͞ob mice to Con A and normalized their lymphocyte and monocyte populations. These results demonstrate that leptin deficiency leads to reduced production of TNF-␣ and IL-18 associated with reduced T cell-mediated hepatotoxicity. In addition, both TNF-␣ and IL-18 appear to be essential mediators of T cell-mediated liver injury.

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Section: Effect Of Exogenous Leptin On Leukocyte Populations In Ob͞obsupporting

confidence: 78%

“…mice) (16)(17)(18)(19). In particular, CD4 ϩ CD8 ϩ were reduced by 59%, CD4 ϩ CD8 Ϫ by 54%, CD4 Ϫ CD8 ϩ by 36%, and CD4 Ϫ CD8 Ϫ by 31% in ob͞ob mice compared with ϩ͞?…”

Section: Effect Of Exogenous Leptin On Leukocyte Populations In Ob͞obmentioning

confidence: 97%

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Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: Role of tumor necrosis factor α and IL-18

Faggioni

Jones-Carson

Reed

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

310

225

View full text Add to dashboard Cite

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“…As in human obesity, obese animals present a delayed wound healing associated with increased polymorphonuclear leukocyte infiltration (15). Acquired immunity is also affected by obesity, because T cell-and B cell-mediated immune responses are impaired in obese ob/ob (16) and diabetic db/db mice (17). Obesity is further characterized by an imbalance of the cytokine network, resulting in a low-grade systemic inflammatory status (18).…”

Section: Impairment Of Dendritic Cell Functionality and Steady-statementioning

confidence: 99%

Impairment of Dendritic Cell Functionality and Steady-State Number in Obese Mice

Macia

Delacre

Abboud

et al. 2006

The Journal of Immunology

123

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There is a finely tuned interplay between immune and neuroendocrine systems. Metabolic disturbances like obesity will have serious consequences on immunity both at the cellular and at the cytokine expression levels. Our in vivo results confirm the immune deficiency of ob/ob mice, leptin deficient and massively obese, characterized by a reduced Ag-specific T cell proliferation after keyhole limpet hemocyanin immunization. In this report, we show that dendritic cells (DCs), major APCs involved in T lymphocyte priming, are affected in obese mice. Both their function and their steady-state number are disturbed. We demonstrate that DCs from ob/ob mice are less potent in stimulation of allogenic T cells in vitro. This impaired functionality is not associated with altered expression of phenotypic markers but with the secretion of immunosuppressive cytokines such as TGF-β. Moreover, we show increased in vivo steady-state number of epidermal DCs in ob/ob mice, which is not due to a migratory defect. The ob/ob mice are characterized by the absence of functional leptin, a key adipokine linking nutrition, metabolism, and immune functions. Interestingly, intradermal injection of leptin is able to restore epidermal DC number in obese mice. Thus, DCs might be directly sensitive to metabolic disturbances, providing a partial explanation of the immunodeficiency associated with obesity.

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“…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.…”

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confidence: 99%

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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Spleen Hemolytic Plaque-Forming Cell Response and Generation of Cytotoxic Cells in Genetically Obese (C57B1/6J <i>ob</i>/<i>ob</i>) Mice

Cited by 34 publications

References 11 publications

Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: Role of tumor necrosis factor α and IL-18

Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: Role of tumor necrosis factor α and IL-18

Impairment of Dendritic Cell Functionality and Steady-State Number in Obese Mice

Leptin: Nourishment for the immune system

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