ArticleDiabetologia2009
The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes.
Article in Diabetologia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Type 2 Diabetes: How Much of an Autoimmune Disease?Frontiers in endocrinology · 2019Pooled it
- A CD40-targeting peptide, OPT501, modulates inflammation in canine diabetes mellitus improving clinical outcomes.Frontiers in immunology · 2026Article
- White Adipocyte Stem Cell Expansion Through Infant Formula Feeding: New Insights into Epigenetic Programming Explaining the Early Protein Hypothesis of Obesity.International journal of molecular sciences · 2025Review
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- Adipocytes control hematopoiesis and inflammation through CD40 signaling.Haematologica · 2023Article
- Beyond energy balance regulation: The underestimated role of adipose tissues in host defense against pathogens.Frontiers in immunology · 2023Review
- Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues.International journal of molecular sciences · 2021Review
- Fat Distribution in Women Is Associated With Depot-Specific Transcriptomic Signatures and Chromatin Structure.Journal of the Endocrine Society · 2020Article
- B Lymphocytes and Adipose Tissue Inflammation.Arteriosclerosis, thrombosis, and vascular biology · 2020Review
- [Association between CD40-CD40L system and obesity in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020Article
- The Adipocyte and Adaptive Immunity.Frontiers in immunology · 2020Review
- Depletion of CD40 on CD11cScientific reports · 2019Article
- Inflammation and Immunity: From an Adipocyte's Perspective.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2019Review
- Adipose-derived stromal/stem cells from different adipose depots in obesity development.World journal of stem cells · 2019Review
- Dichotomous roles of co-stimulatory molecules in diabetes mellitus.Oncotarget · 2018Review
- Regulation, Communication, and Functional Roles of Adipose Tissue-Resident CD4Frontiers in immunology · 2018Review
- Article
- Article
- CD40-mediated signalling influences trafficking, T-cell receptor expression, and T-cell pathogenesis, in the NOD model of type 1 diabetes.Immunology · 2017Article
- Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors.Molecular metabolism · 2017Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisObesity 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.
methodsCD40 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.
resultsCD40 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/
interpretationAdipocyte 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.
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