Agonist anti-ChemR23 mAb reduces tissue neutrophil accumulation and triggers chronic inflammation resolution - Inria - Institut national de recherche en sciences et technologies du numérique Access content directly
Journal Articles Science Advances Year : 2021

Agonist anti-ChemR23 mAb reduces tissue neutrophil accumulation and triggers chronic inflammation resolution

V. Gauttier
G. Robert-Siegwald
G. Chêne
  • Function : Author
M. Dubourdeau
B. Vanhove
N. Poirier

Abstract

Resolution of inflammation is elicited by proresolving lipids, which activate GPCRs to induce neutrophil apoptosis, reduce neutrophil tissue recruitment, and promote macrophage efferocytosis. Transcriptional analyses in up to 300 patients with Inflammatory Bowel Disease (IBD) identified potential therapeutic targets mediating chronic inflammation. We found that ChemR23, a GPCR targeted by resolvin E1, is overexpressed in inflamed colon tissues of severe IBD patients unresponsive to anti-TNF alpha or anti-alpha 4 beta 7 therapies and associated with significant mucosal neutrophil accumulation. We also identified an anti-ChemR23 agonist antibody that induces receptor signaling, promotes macrophage efferocytosis, and reduces neutrophil apoptosis at the site of inflammation. This ChemR23 mAb accelerated acute inflammation resolution and triggered resolution in ongoing chronic colitis models, with a significant decrease in tissue lesions, fibrosis and inflammation-driven tumors. Our findings suggest that failure of current IBD therapies may be associated with neutrophil infiltration and that ChemR23 is a promising therapeutic target for chronic inflammation.

Dates and versions

hal-03462811 , version 1 (02-12-2021)

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C. Trilleaud, V. Gauttier, K. Biteau, I. Girault, L. Belarif, et al.. Agonist anti-ChemR23 mAb reduces tissue neutrophil accumulation and triggers chronic inflammation resolution. Science Advances , 2021, 7 (14), pp.1-14. ⟨10.1126/sciadv.abd1453⟩. ⟨hal-03462811⟩
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