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Neutralization of pro‐inflammatory monocytes by targeting TLR2 dimerization ameliorates colitis
Author(s) -
ShmuelGalia Liraz,
Aychek Tegest,
Fink Avner,
Porat Ziv,
Zarmi Batya,
Bernshtein Biana,
Brenner Ori,
Jung Steffen,
Shai Yechiel
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201592649
Subject(s) - biology , neutralization , colitis , virology , monocyte , immunology , tlr2 , inflammation , antibody , tlr4
Monocytes have emerged as critical driving force of acute inflammation. Here, we show that inhibition of Toll‐like receptor 2( TLR 2) dimerization by a TLR 2 transmembrane peptide ( TLR 2‐p) ameliorated DSS ‐induced colitis by interfering specifically with the activation of Ly6C + monocytes without affecting their recruitment to the colon. We report that TLR 2‐p directly interacts with TLR 2 within the membrane, leading to inhibition of TLR 2– TLR 6/1 assembly induced by natural ligands. This was associated with decreased levels of extracellular signal‐regulated kinases ( ERK ) signaling and reduced secretion of pro‐inflammatory cytokines, such as interleukin ( IL )‐6, IL ‐23, IL ‐12, and IL ‐1β. Altogether, our study provides insights into the essential role of TLR 2 dimerization in the activation of pathogenic pro‐inflammatory Ly6C hi monocytes and suggests that inhibition of this aggregation by TLR 2‐p might have therapeutic potential in the treatment of acute gut inflammation.