title: Macrophages participate in IL-17-mediated inflammation.
abstract: The involvement of macrophages (MΦs) in Th17-cell responses is still poorly understood. While neutrophils are thought to be the predominant effector of Th17-cell responses, IL-17 is also known to induce myelotropic chemokines and growth factors. Other T-cell-derived cytokines induce non-classical functions, suggesting that IL-17 sigxnaling may similarly elicit unique MΦ functions. Here, we characterized the expression of subunits of the IL-17 receptor on primary murine MΦs from different anatomical compartments. The greatest expression of IL-17 receptors was observed on mucosal Ly6C(hi)  "inflammatory" MΦs. We further observed upregulation of IL-17 receptors in vitro on bone marrow-derived macrophages (BMMΦs) in response to peptidoglycan or CpG oligonucleotide stimuli, and in vivo, upon CFA administration. Macrophages expressing IL-17 receptors were observed infiltrating the hearts of mice with myocarditis, and genetic ablation of IL-17RA altered MΦ recruitment. Treating primary MΦs from a wide variety of different anatomic sources (as well as cell lines) with IL-17A induced the production of unique profiles of cytokines and chemokines, including GM-CSF, IL-3, IL-9, CCL4/MIP-1β and CCL5/RANTES. IL-17A also induced production of IL-12p70; IL-17-signaling-deficient MΦs elicited diminished IFN-γ production by responding DO11.10 CD4(+)  T cells when used as APCs. These data indicate that MΦs from different anatomic locations direct IL-17-mediated responses.
authors.affiliation: Training Program in Immunology, Johns Hopkins University School of Medicine, Boltimore, MD, USA. jbarin@jhmi.edu
authors.forename: Jobert G
authors.initials: JG
authors.lastname: Barin
authors.forename: G Christian
authors.initials: GC
authors.lastname: Baldeviano
authors.forename: Monica V
authors.initials: MV
authors.lastname: Talor
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.forename: Sufey
authors.initials: S
authors.lastname: Ong
authors.forename: Farhan
authors.initials: F
authors.lastname: Quader
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Zheng
authors.forename: Patrizio
authors.initials: P
authors.lastname: Caturegli
authors.forename: Noel R
authors.initials: NR
authors.lastname: Rose
authors.forename: Daniela
authors.initials: D
authors.lastname: Ciháková
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation / Q000276:immunology
chemical_list: D018925:Chemokines; D020381:Interleukin-17; D053722:Receptors, Interleukin-17