Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion

摘要: Microenvironment molecular cues direct T helper (Th) cell differentiation; however, Th17 fate determination is still imprecisely understood in humans. To assess the role of prostaglandin E2 (PGE2) Th expansion, we activated peripheral blood mononuclear cells by CD3 cross-linking. In presence exogenous PGE2, produced higher interleukin-17 (IL-17), C-C chemokine ligand 20 (CCL20)/macrophage inflammatory protein 3α (MIP-3α), CXC 8 (CXCL8)/IL-8, and lower interferon-γ IL-22 levels than control cultures. Exogenous PGE2 IL-23 synergized inducing IL-17, whereas indomethacin blockade drastically reduced IL-17 but not production. Furthermore, IL-1 tumor necrosis factor was absolutely required for doubled frequency CD4+ producing within subset enhanced receptor 6 (CCR6) CCR4 while decreasing 3 (CXCR3) expression. T-cell lines, production segregated with CCR6+ subset. compared CXCR3+ cells, monocytes/macrophages much matrix metalloproteinase-1, -3, -9 similar CXCL10 IL-1β. These results identify as participating expansion endowed high capacity, which turn favors monocyte mediators important host defense tissue destruction.