Macrophage responses to interleukin-17 are regulated by location and inflammation (37.35)

Abstract The purpose of this study was to examine how macrophage-lineage cells participate in T helper 17 (Th17)-mediated inflammatory responses. We were interested in how this response may be affected by compartmentalization, and the presence of an inflammatory microenvirionment. We isolated primary murine F4/80+ macrophages (Mϕ) from a broad variety of compartments including spleen, peripheral blood, peritoneum, gut, lung, liver, and CNS. We assayed the expression of the receptors IL17RA and IL17RC on these cells by flow cytometric methods, and observed the highest levels of IL17RA and IL17RC expression on Mϕ associated with mucosal surfaces, particularly gut and lung. In order to examine the influence of inflammatory stimuli on the expression of IL17RA and IL17RC in vitro, bone marrow-derived macrophages, which express low levels of IL17RA and IL17RC were stimulated with combinations of TLR ligands, and proinflammatory cytokines. We observed coordinate expression of both IL17 receptor subunits controlled by TNFα and peptidoglycan signaling. Following encounter with CFA adjuvant in vivo, the expression of both IL17RA and IL17RC was most dramatically increased on Mϕ in the liver. We further wished to determine biological consequences of IL17 signaling, and have begun to identify genes regulated by IL17 in macrophage-lineage cells. Together, these data indicate that macrophages participate in Th17-mediated immunity in a manner regulated by localization and inflammation.