Neutralization of pro‐inflammatory monocytes by targeting TLR2 dimerization ameliorates colitis |
| |
| Authors: | Avner Fink Ziv Porat Batya Zarmi Biana Bernshtein Ori Brenner Steffen Jung Yechiel Shai |
| |
| Affiliation: | 1. Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel;2. Department of Biological Services, The Weizmann Institute of Science, Rehovot, Israel;3. Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel;4. Department of Veterinary Resources, The Weizmann Institute of Science, Rehovot, Israel |
| |
| Abstract: | Monocytes have emerged as critical driving force of acute inflammation. Here, we show that inhibition of Toll‐like receptor 2(TLR2) dimerization by a TLR2 transmembrane peptide (TLR2‐p) ameliorated DSS‐induced colitis by interfering specifically with the activation of Ly6C+ monocytes without affecting their recruitment to the colon. We report that TLR2‐p directly interacts with TLR2 within the membrane, leading to inhibition of TLR2–TLR6/1 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 TLR2 dimerization in the activation of pathogenic pro‐inflammatory Ly6Chi monocytes and suggests that inhibition of this aggregation by TLR2‐p might have therapeutic potential in the treatment of acute gut inflammation. |
| |
| Keywords: | colitis monocytes TLR2 Toll‐like receptor |
|
|
