Antagonism between MyD88- and TRIF-dependent signals in B7RP-1 up-regulation

作者：Zhou ZP; Hoebe K; Du X; Jiang ZF^*; Shamel L; Beutler B^*

来源：European Journal of Immunology, 2005, 35(6): 1918-1927.

DOI：10.1002/eji.200525971

• toll-like receptor
• type IIFN
• B7RP-1
• macrophages
• B cells

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 upregulation of CD80 (B7.1) and CD86 (137.2) 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 137 costimulatory family members and suggest that they may act to limit B7RP-1 expression and thus limit signals derived from 137RP-1-ICOS interaction.

• 出版日期2005-6