Macrophages participate in IL-17-mediated inflammation.

ABSTRACT: The involvement of macrophages (M?s) 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 M? functions. Here, we characterized the expression of subunits of the IL-17 receptor on primary murine M?s from different anatomical compartments. The greatest expression of IL-17 receptors was observed on mucosal Ly6C(hi) "inflammatory" M?s. We further observed upregulation of IL-17 receptors in vitro on bone marrow-derived macrophages (BMM?s) 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 M? recruitment. Treating primary M?s 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-1? and CCL5/RANTES. IL-17A also induced production of IL-12p70; IL-17-signaling-deficient M?s elicited diminished IFN-? production by responding DO11.10 CD4(+) T cells when used as APCs. These data indicate that M?s from different anatomic locations direct IL-17-mediated responses.

SUBMITTER: Barin JG 

PROVIDER: S-EPMC4292791 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature