title: Antagonism between MyD88- and TRIF-dependent signals in B7RP-1 up-regulation.
abstract: Type I interferons (IFN) play a critical role in the Toll-like receptor (TLR)-mediated expression of B7 costimulatory family members. For example, LPS-induced up-regulation of CD80 (B7.1) and CD86 (B7.2) is abrogated in antigen-presenting cells (APC) deficient in TRIF or TRAM, two adaptors that are responsible for TLR4-mediated production of Type I IFN. In this report, we demonstrate that LPS-induced up-regulation of B7-related protein 1 (B7RP-1), a ligand for ICOS, is dependent primarily upon the MyD88-dependent signaling pathway. Signaling via the TRIF pathway sharply limits MyD88-dependent B7RP-1 up-regulation. Hence, LPS induces significantly higher B7RP-1 expression on TRIF- or TRAM-deficient mouse peritoneal macrophages and on TRIF-deficient mouse splenic B cells as compared to wild-type cells. Further studies reveal that Type I IFN are general suppressors of TLR-mediated up-regulation of B7RP-1. These data indicate that Type I IFN play a dual role in the TLR-mediated expression of B7 costimulatory family members and suggest that they may act to limit B7RP-1 expression and thus limit signals derived from B7RP-1-ICOS interaction.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhou
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.forename: Zhengfan
authors.initials: Z
authors.lastname: Jiang
authors.forename: Louis
authors.initials: L
authors.lastname: Shamel
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology*; D018122:B7-1 Antigen / Q000235:genetics*; D005786:Gene Expression Regulation; D060945:Inducible T-Cell Co-Stimulator Ligand; D016899:Interferon-beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88; D011070:Poly I-C / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060945:Inducible T-Cell Co-Stimulator Ligand; D016899:Interferon-beta; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D011070:Poly I-C; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse