CD40 and Its Ligand in Atherosclerosis

Lutgens, Esther; Lievens, Dirk; Beckers, Linda; Donners, Marjo M. P. C.; Daemen, Mat J.A.P.

doi:10.1016/j.tcm.2007.02.004

Cited by 109 publications

(97 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CD40 lacks intrinsic kinase activity in the cytoplasmic domain but activates NF-κB transcription factor through association with TNF-receptor associated factors (TRAF), a family of adaptator proteins [36]. CD40 can bind five of the six TRAF family members (TRAF1, −2, −3, −5, −6) depending on cell type or function [37]. Interestingly, TRAF6 is expressed in human adipocytes [38] and may participate to CD40 signalling in adipocytes.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

Aims/hypothesis Obesity is associated with adipose tissue inflammation. The CD40 molecule, TNF receptor superfamily member 5 (CD40)/CD40 ligand (CD40L) pathway plays a role in the onset and maintenance of the inflammatory reaction, but has not been studied in human adipose tissue. Our aim was to examine CD40 expression by human adipocytes and its participation in adipose tissue inflammation. Methods CD40 expression was investigated in human whole adipose tissue and during adipocyte differentiation by real-time PCR, Western blot and immunohistochemistry. The CD40/CD40L pathway was studied using recombinant CD40L (rCD40L) in adipocyte culture and neutralising antibodies in lymphocyte/adipocyte co-culture. Results CD40 mRNA levels in subcutaneous adipose tissue were higher in the adipocyte than in the stromal-vascular fraction. CD40 expression was upregulated during adipocyte differentiation. Addition of rCD40L to adipocytes induced mitogen activated protein kinase (MAPK) activation, stimulated inflammatory adipocytokine production, and decreased insulin-induced glucose transport in parallel with a downregulation of IRS1 and GLUT4 (also known as SCL2A4). rCD40L decreased the expression of lipogenic genes and increased lipolysis. CD40 mRNA levels were significantly higher in subcutaneous adipose tissue than in visceral adipose tissue of obese patients and were positively correlated with BMI, and with IL6 and leptin mRNA levels. Lymphocyte/adipocyte co-culture led to an upregulation of proinflammatory adipocytokines and a downregulation of leptin and adiponectin. Physical separation of the two cell types attenuated these effects, suggesting the involvement of a cell-cell contact. Blocking the CD40/CD40L interaction with neutralising antibodies reduced IL-6 secretion from adipocytes. Conclusions/interpretation Adipocyte CD40 may contribute to obesity-related inflammation and insulin resistance. T lymphocytes regulate adipocytokine production through both the release of soluble factor(s) and heterotypic contact with adipocytes involving CD40.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Indeed, preclinical assessment of the efficacy of blocking the CD40-CD154 interaction is either ongoing in several autoimmune disease models, such as multiple sclerosis 61 and lupus erythematosus, 62 or is being considered for cardiovascular disease 63,64 and to achieve immunologic tolerance in transplantation. 65 Our comparative transcriptional profiling study highlights the specificity and efficiency of the siRNA anti-CD40 modulating CD40 expression and function in ECs, which supports its anti-inflammatory potential.…”

Section: Discussionmentioning

confidence: 99%

CD40: an upstream master switch for endothelial cell activation uncovered by RNAi-coupled transcriptional profiling

Pluvinet

Olivar

Krupiński

et al. 2008

Blood

View full text Add to dashboard Cite

“…Treatment of Apoe 2/2 mice with a plasmid encoding the endogenous IL-18 inhibitor, IL-18 binding protein (15), or genetic deletion of IL-18 (16), significantly reduces lesion development, whereas exogenous administration of IL-18 clearly accelerates disease progression (17,18). CD40-CD40L interactions also promote Th1 cell development, and inhibition of this pathway reduces lesion development and induces a 'stableʼ plaque phenotype [reviewed in (19)]. However, T cell-independent effects may be involved in this pathway, because CD40L deficiency in bone marrowderived cells did not alter atherosclerosis.…”

Section: Th1 Response In Atherosclerosismentioning

confidence: 99%

The role of adaptive T cell immunity in atherosclerosis

Mallat

Taleb

Ait‐Oufella

et al. 2009

Journal of Lipid Research

182

139

View full text Add to dashboard Cite

There is now solid evidence that T cell adaptive immunity is involved in atherogenesis. While initial studies have focused on the pathogenic arm of the immune response, more recent work clearly suggests an important role for several subsets of regulatory T cells in the protection against lesion development. Here, we review the current knowledge on the role of both pathogenic and regulatory adaptive T cell immunity in atherosclerosis, generated mainly from the study of mouse models of the disease.-Mallat, Z., S. Taleb, H. Ait-Oufella, and A. Tedgui. The role of adaptive T cell immunity in atherosclerosis. J. Lipid Res. 2009. 50: S364-S369.

show abstract

CD40 and Its Ligand in Atherosclerosis

Cited by 109 publications

References 41 publications

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

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

CD40: an upstream master switch for endothelial cell activation uncovered by RNAi-coupled transcriptional profiling

The role of adaptive T cell immunity in atherosclerosis

Contact Info

Product

Resources

About