title: Differential regulation of chemokine production by Fcgamma receptor engagement in human monocytes: association of CCL1 with a distinct form of M2 monocyte activation (M2b, Type 2).
abstract: CC chemokine ligand 1 (CCL1; I-309) is a CC chemokine that interacts with CC chemokine receptor 8, which is preferentially expressed in polarized T helper cell type 2 and Tc2 cells, in eosinophils, and in T regulatory cells. The present study, prompted by transcriptional profiling of human monocytes undergoing different forms of activation, was designed to characterize the production of CCL1 in monocytes compared with the production of other chemokines (CCL2, CCL22, and CCL18) differentially regulated by distinct activation signals. Lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), interleukin (IL)-1beta, tumor necrosis factor alpha, IL-4, IL-13, IL-10, IL-6, IL-18, and combinations thereof did not induce CCL1 production in monocytes, and some of these signals stimulated production of reference chemokines. Induction of CCL1 in monocytes required engagement of Fc receptor for immunoglobulin G (FcgammaR)II and exposure to IL-1beta or LPS. This combination of stimuli results in a form of M2 (M2b, Type 2) macrophage activation. FcgammaR engagement also induced CCL22 and amplified its stimulation by IL-4. In contrast, FcgammaR stimulation inhibited the IL-10- and LPS-mediated induction of CCL18. IL-10, IL-4, and IFN-gamma inhibited induction of CCL1 by FcgammaR ligation and IL-1beta. CCL1 was present in synovial fluids and macrophages in juvenile idiopathic arthritis. Thus, regulation of CCL1 in human monocytes is unique, with an obligate requirement of FcgammaR engagement and costimulation by signals (IL-1beta and LPS), which use the myeloid differentiation primary-response protein 88 adaptor protein. Thus, CCL1 is a CC chemokine with a unique pattern of regulation associated with a distinct form of M2 (Type 2, M2b) monocyte activation, which participates in macrophage-dependent regulatory circuits of innate and adaptive immunity.
authors.affiliation: Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Sironi
authors.forename: Fernando O
authors.initials: FO
authors.lastname: Martinez
authors.forename: Daniele
authors.initials: D
authors.lastname: D'Ambrosio
authors.forename: Marco
authors.initials: M
authors.lastname: Gattorno
authors.forename: Nadia
authors.initials: N
authors.lastname: Polentarutti
authors.forename: Massimo
authors.initials: M
authors.lastname: Locati
authors.forename: Andrea
authors.initials: A
authors.lastname: Gregorio
authors.forename: Andrea
authors.initials: A
authors.lastname: Iellem
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cassatella
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Francesco
authors.initials: F
authors.lastname: Sinigaglia
authors.forename: Annunciata
authors.initials: A
authors.lastname: Vecchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D001171:Arthritis, Juvenile / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D054402:Chemokine CCL1; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000502:physiology*; D005810:Multigene Family; D017452:Receptors, IgG / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: C065971:CCL1 protein, human; D054402:Chemokine CCL1; D018925:Chemokines; D019742:Chemokines, CC; D017452:Receptors, IgG