title: CD40L stimulates the crosstalk between adipocytes and inflammatory cells.
abstract: Macrophages and lymphocytes are implicated in obesity-related adipose tissue inflammation via interactions with adipocytes. Co-stimulatory systems, especially the CD40-CD40L system, play an important role in T cell activation and inflammatory reactions. CD40L was recently shown to promote adipose tissue inflammation in vivo, yet, the mechanisms underlying its function in the intercellular communication between inflammatory cells and adipocytes remain not entirely clear. Here we found that adipocyte stimulation with CD40L increased the expression of CD40, as well as of chemokines, such as MCP-1, CCL4, or CCL5, whereas adipocyte CD40 expression was also stimulated by TNF but not palmitate. Moreover, conditioned media of CD40L-pretreated adipocytes provoked elevated migration of mononuclear cells and increased the expression of inflammatory genes in bone marrow derived mononuclear phagocytes (BMDM) shifting them to an M1-like pro-inflammatory phenotype. Nonetheless, the CD40/CD40L interaction did not contribute to the adhesion between adipocytes and T cells. Together, CD40L stimulates adipocyte chemokine expression, thereby attracting monocytes/macrophages into the adipose tissue. Moreover, CD40L stimulation of adipocytes likely promotes macrophage M1 polarization in the adipose tissue and thereby perpetuation of adipose tissue inflammation.
authors.affiliation: Department of Internal Medicine III, University of Dresden, -Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Chatzigeorgiou
authors.forename: J
authors.initials: J
authors.lastname: Phieler
authors.forename: J
authors.initials: J
authors.lastname: Gebler
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: T
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D023201:CD40 Ligand / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D017077:Culture Media, Conditioned; D023201:CD40 Ligand; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor