The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes

Poggi, Marjorie; Jager, Jennifer; Paulmyer‐Lacroix, Odile; Peiretti, Franck; Grémeaux, Thierry; Verdier, Monique; Grino, Michel; Stépanian, Alain; Msika, Simon; Burcelin, Rémy; Prost, Dominique de; Tanti, Jean‐François; Alessi, Marie‐Christine

doi:10.1007/s00125-009-1267-1

Cited by 108 publications

(112 citation statements)

References 43 publications

(50 reference statements)

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“…CD40-CD40L interactions induce T-cell and APC activation, cytokine production, and B-cell isotype class switching as well as endothelial cell activation and monocyte migration (32,38,39,56). The expression of CD40 on AT cells, including adipocytes, stromal AT cells, and immune cells, positively correlates with BMI (57). Although the expression of membrane-bound CD40L is restricted to immune cells and stromal cells within the AT, soluble CD40L (sCD40L), mainly derived from activated platelets and T cells, may also activate CD40 + adipocytes (38,39,57).…”

Section: Cd40-cd40lmentioning

confidence: 99%

“…The expression of CD40 on AT cells, including adipocytes, stromal AT cells, and immune cells, positively correlates with BMI (57). Although the expression of membrane-bound CD40L is restricted to immune cells and stromal cells within the AT, soluble CD40L (sCD40L), mainly derived from activated platelets and T cells, may also activate CD40 + adipocytes (38,39,57). Clinical studies have demonstrated that sCD40L plasma levels are increased in obese patients and positively correlate with BMI, waist circumference, fasting glucose, and leukocyte counts and that sCD40L levels decrease after bariatric surgery (58).…”

Section: Cd40-cd40lmentioning

confidence: 99%

“…Clinical studies have demonstrated that sCD40L plasma levels are increased in obese patients and positively correlate with BMI, waist circumference, fasting glucose, and leukocyte counts and that sCD40L levels decrease after bariatric surgery (58). CD40 ligation on adipocytes results in activation of classical proinflammatory signal transduction pathways, including extracellular signal-related kinase, p38, Jun NH 2 -terminal kinase, mitogen-activated protein kinase, and nuclear factor-kB (NF-kB), which results in the expression of cytokines and chemokines, including TNF, IL-6, and MCP-1, as well as the prothrombotic mediator plasminogen activator inhibitor 1 (57,59,60). These proinflammatory mediators subsequently activate endothelial cells and immune cells, which promote a generalized proinflammatory AT status.…”

Section: Cd40-cd40lmentioning

confidence: 99%

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Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

et al. 2014

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In the past two decades, numerous experimental and clinical studies have established the importance of inflammation and immunity in the development of obesity and its metabolic complications, including insulin resistance and type 2 diabetes mellitus. In this context, T cells orchestrate inflammatory processes in metabolic organs, such as the adipose tissue (AT) and liver, thereby mediating obesity-related metabolic deterioration. Costimulatory molecules, which are present on antigen-presenting cells and naïve T cells in the AT, are known to mediate the crosstalk between the adaptive and innate immune system and to direct T-cell responses in inflammation. In this Perspectives in Diabetes article, we highlight the newest insights in immune cell interactions in obesity and discuss the role of costimulatory dyads in its pathogenesis. Moreover, the potential of therapeutic strategies that target costimulatory molecules in the metabolic syndrome is explored.

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Section: Cd40-cd40lmentioning

confidence: 99%

Section: Cd40-cd40lmentioning

confidence: 99%

Section: Cd40-cd40lmentioning

confidence: 99%

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Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

et al. 2014

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“…After 48 h (d0), the medium was removed and replaced by Dulbecco's modified Eagle's medium containing 2 mM insulin only. Human subcutaneous preadipocytes and mouse embryonic fibroblasts were obtained as already described (19,20). Human visceral preadipocytes were from Lonza (Levallois-Perret, France).…”

Section: Cell Culture Differentiation and Transfectionmentioning

confidence: 99%

Down-regulation of Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) Expression Is Necessary for Adipocyte Differentiation

Bernot¹,

Barruet²,

Poggi

et al. 2010

Journal of Biological Chemistry

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Matrix metalloproteinase activity is essential for proper extracellular matrix remodeling that takes place during adipose tissue formation. Four tissue inhibitors of matrix metalloproteinases (TIMPs) regulate their activity. However, the role of TIMPs in adipocyte differentiation is poorly understood. We found that the expression of all TIMPs was modified during adipocyte differentiation, but that of TIMP-3 was distinguished by its extreme down-regulation. TIMP-3 expression was closely linked to the differentiation process. Indeed, it remained low during the adipocyte differentiation but increased when cell differentiation was prevented. We identified the transcription factor Sp1 as being responsible for the regulation of TIMP-3 expression during adipocyte differentiation. Overexpression of TIMP-3 reduced adipocyte differentiation, underlining its active role in this process. TIMP-3 overexpression decreased the expression of the early and obligate key inductors of adipogenesis Krüppel-like factor 4 (Klf4), early growth response 2 (Egr2/ Krox20), and CAAT/enhancer-binding protein ␤ (C/EBP␤). Our results indicate that during preadipocyte differentiation, the Sp1-dependent decrease in TIMP-3 expression is required for the successful implementation of the adipocyte differentiation program.Development of obesity is associated with extensive modifications of the composition and architecture of the adipose tissue. These events necessitate dynamic changes of cell-matrix interactions and extracellular matrix remodeling that are made possible by the alteration of pericellular proteolytic activities. Normal turnover of the extracellular matrix is regulated by the opposing activities of proteinases and their inhibitors (1, 2).Matrix metalloproteinases (MMPs) 4 are a family of Ͼ20 secreted zinc-dependent proteinases involved in the extracellular matrix degradation, the release of sequestered growth fac-

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“…This allows for substantial cross-talk between these different cell types though cell-cell contact, surface molecular receptors and secreted factors. This communication between the cells is essential for the normal functioning of adipose tissue and this complex-reciprocal signaling has been demonstrated by in vitro co-culture experiments [5][6][7]. We have previously demonstrated that unique secretion profiles can be obtained from different adipose-derived cell populations [8].…”

Section: Introductionmentioning

confidence: 91%

Treatment of a mouse model of collagen antibody-induced arthritis with human adipose-derived secretions

Blaber¹,

Webster²,

Breen³

et al. 2013

OJRM

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The use of adipose-derived cells as a treatment for a variety of diseases is becoming increasingly common. These therapies include the use of cultured mesenchymal stem cells (MSCs) and freshly isolated stromal vascular fraction (SVF) alone, or in conjunction with other cells such as adipocytes. There is a substantial amount of literature published on the therapeutic properties of MSCs and their secretions as the main driver of their therapeutic effect. However, there is little data available on the therapeutic potential of secretions from SVF, either with or without adipocytes. We investigated the ability of secretions from human adipose SVF alone and the SVF co-cultured with adipocytes as a proxy for cell therapy, to ameliorate an inflammatory disorder. This ethics approved study involved the treatment of collagen antibody-induced arthritis (CAIA) in mice with secretions from SVF, SVF co-cultured with adipocytes, or a vehicle control via both intravenous (IV) and intramuscular (IM) routes. Treatment outcome was assessed by paw volume, ankle size and clinical arthritis score measurements. Serum samples were obtained following euthanasia and analysed for a panel of 32 mouse cytokines and growth factors. The dose and timing regime used for the IM administration of both human secretion mixtures did not significantly ameliorate arthritis in this model. The IV administration of SVF adipocyte co-culture secretions reduced the paw volume, and significantly reduced the ankle size and clinical arthritis score when compared to the IV vehicle control mice. This was a superior therapeutic effect than treatment with SVF secretions. Furthermore, treatment with SVF adipocyte coculture secretions resulted in a significant reduction in serum levels of key cytokines, IL-2 and VEGF, involved in the pathogenesis of rheumatoid arthritis. Therefore, the SVF cocultured with adipocytes is an attractive therapeutic for inflammatory conditions.

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The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes

Cited by 108 publications

References 43 publications

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

Immune Cell Crosstalk in Obesity: A Key Role for Costimulation?

Down-regulation of Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) Expression Is Necessary for Adipocyte Differentiation

Treatment of a mouse model of collagen antibody-induced arthritis with human adipose-derived secretions

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