Down modulation of human TLR3 function by a monoclonal antibody.

Abstract:

:Toll-like receptors are a family of pattern-recognition receptors that contribute to the innate immune response. Toll-like receptor 3 (TLR3) signals in response to foreign, endogenous and synthetic ligands including viral dsRNA, bacterial RNA, mitochondrial RNA, endogenous necrotic cell mRNA and the synthetic dsRNA analog, poly(I:C). We have generated a monoclonal antibody (mAb CNTO2424) that recognizes the extracellular domain (ECD) of human TLR3 in a conformation-dependent manner. CNTO2424 down-regulates poly(I:C)-induced production of IL-6, IL-8, MCP-1, RANTES, and IP-10 in human lung epithelial cells. In addition, mAb CNTO2424 was able to interfere with the known TLR3-dependent signaling pathways, namely NF-kappaB, IRF-3/ISRE, and p38 MAPK. The generation of this neutralizing anti-TLR3 mAb provides a unique tool to better understand TLR3 signaling and potential cross-talk between TLR3 and other molecules.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Duffy KE,Lamb RJ,San Mateo LR,Jordan JL,Canziani G,Brigham-Burke M,Korteweg J,Cunningham M,Beck HS,Carton J,Giles-Komar J,Duchala C,Sarisky RT,Mbow ML

doi

10.1016/j.cellimm.2007.10.002

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

103-14

issue

2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(07)00203-1

journal_volume

248

pub_type

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