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

Zuping Zhou, Kasper Hoebe, Xin Du, Zhengfan Jiang, Louis Shamel, Bruce Beutler

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1918-1927
Number of pages10
JournalEuropean Journal of Immunology
Issue number6
StatePublished - Jun 2005


  • B cells
  • B7RP-1
  • Macrophages
  • Toll-like receptor
  • Type I IFN

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Antagonism between MyD88- and TRIF-dependent signals in B7RP-1 up-regulation'. Together they form a unique fingerprint.

Cite this