Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling-dependent CD8 T-cell activation.

Abstract:

:Class A scavenger receptor (SRA), also known as CD204, has been shown to participate in the pathogenesis of atherosclerosis and the pattern recognition of pathogen infection. However, its role in adaptive immune responses has not been well defined. In this study, we report that the lack of SRA/CD204 promotes Toll-like receptor (TLR)4 agonist-augmented tumor-protective immunity, which is associated with enhanced activation of CD8(+) effector T cell and improved inhibition of tumor growth. Dendritic cells (DCs) deficient in SRA/CD204 display more effective immunostimulatory activities upon TLR4 engagement than those from wild-type counterparts. Silencing of SRA/CD204 by RNA interference improves the ability of DCs to prime antigen-specific CD8(+) T cells, suggesting that antigen-presenting cells, for example, DCs, play a major role in SRA/CD204-mediated immune modulation. Our findings reveal a previously unrecognized role for SRA/CD204, a non-TLR pattern recognition receptor, as a physiologic negative regulator of TLR4-mediated immune consequences, which has important clinical implications for development of TLR-targeted immunotherapeutic intervention.

journal_name

Blood

journal_title

Blood

authors

Yi H,Yu X,Gao P,Wang Y,Baek SH,Chen X,Kim HL,Subjeck JR,Wang XY

doi

10.1182/blood-2008-11-190033

subject

Has Abstract

pub_date

2009-06-04 00:00:00

pages

5819-28

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2008-11-190033

journal_volume

113

pub_type

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