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

被引：19

作者：

Zhou, ZP ^{[1
]}

Hoebe, K ^{[1
]}

Du, X ^{[1
]}

Jiang, ZF ^{[1
]}

Shamel, L ^{[1
]}

Beutler, B ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2005年 / 35卷 / 06期

关键词：

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

D O I：

10.1002/eji.200525971

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1918 / 1927

页数：10

共 48 条

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