title: Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation.
abstract: Toll-like receptors (TLRs) are critical components of innate immunity and function as rapid pathogen sensors. TLR4 is expressed on CD4(+) T cells as well, the functional significance of which is unclear. In this study, we analyzed the function of TLR4 in T cells but did not find a role in promoting T helper (Th) cell polarization. Instead, TLR4 ligation enhanced both CD4(+) T-cell proliferation and survival in vitro. Using the experimental autoimmune encephalomyelitis (EAE) model, we found that the loss of TLR4 solely in CD4(+) T cells almost completely abrogated disease symptoms, mainly through blunted Th17 and, to a lesser degree, Th1 responses. Moreover, Tlr4(-/-) γδ T cells were defective in IL-17 and IFN-γ production following EAE induction. This study supports an important role of this innate receptor in the direct regulation of T-cell activation and survival during autoimmune inflammation.
authors: Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054, USA.
authors: Joseph M
authors: JM
authors: Reynolds
authors: Gustavo J
authors: GJ
authors: Martinez
authors: Yeonseok
authors: Y
authors: Chung
authors: Chen
authors: C
authors: Dong
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C064658:RAG-1 protein; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin