title: Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production.
abstract: C-type lectins are pattern-recognition receptors important for pathogen binding and uptake by APCs. Evidence is accumulating that integration of incoming cellular signals in APCs is regulated by grouping of receptors and signaling molecules into organized membrane complexes, such as lipid rafts and tetraspanin microdomains. In this study, we demonstrate that C-type lectin dectin-1 functionally interacts with leukocyte-specific tetraspanin CD37. Dectin-1 and CD37 colocalize on the surface of human APCs. Importantly, macrophages of CD37-deficient (CD37(-/-)) mice express decreased dectin-1 membrane levels, due to increased dectin-1 internalization. Furthermore, transfection of CD37 into a macrophage cell line elevated endogenous dectin-1 surface expression. Although CD37 deficiency does not affect dectin-1-mediated phagocytosis, we observed a striking 10-fold increase of dectin-1-induced IL-6 production in CD37(-/-) macrophages compared with wild-type cells, despite reduced dectin-1 cell surface expression. Importantly, the observed increase in IL-6 production was specific for dectin-1, because signaling via other pattern-recognition receptors was unaffected in CD37(-/-) macrophages and because the dectin-1 ligand curdlan was used. Taken together, these findings show that tetraspanin CD37 is important for dectin-1 stabilization in APC membranes and controls dectin-1-mediated IL-6 production.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Friederike
authors.initials: F
authors.lastname: Meyer-Wentrup
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Marleen
authors.initials: M
authors.lastname: Ansems
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wright
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
authors.forename: Annemiek B
authors.initials: AB
authors.lastname: van Spriel
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D059470:Tetraspanins; D000099181:Dectin-1; D000093242:Interleukin-6 Inhibitors
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D015850:Interleukin-6; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D059470:Tetraspanins; D000099181:Dectin-1; D000093242:Interleukin-6 Inhibitors; C059071:CD37 protein, human; C504565:Cd37 protein, mouse