Lack of protective effect of CCR3 blockade during experimental colitis may be related to CCR3 expression by colonic Tregs.
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ABSTRACT:
SUBMITTER: Ferhat M
PROVIDER: S-EPMC8236119 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
Lack of protective effect of CCR3 blockade during experimental colitis may be related to CCR3 expression by colonic Tregs.
Ferhat Maroua M Hablot Julie J Taieb Mahdia M Salem Fatouma F Netter Patrick P Peyrin-Biroulet Laurent L Jouzeau Jean-Yves JY Moulin David D
Clinical and translational medicine 20210601 6
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Project description:Background and aimsAcute severe steroid-refractory ulcerative colitis remains a medically challenging condition with frequent need of surgery. It can be treated with the calcineurin inhibitor cyclosporine A with the need for therapeutic drug monitoring and significant toxicity. Recently, a novel calcineurin inhibitor, voclosporin, has been approved for the treatment of lupus nephritis with no need for therapeutic drug monitoring and an improved long-term safety profile. However, the therapeutic effect of voclosporin in acute severe steroid-refractory ulcerative colitis is still uncertain. We aimed to assess the therapeutic potential of voclosporin to ameliorate inflammation in an experimental model of colitis.MethodsWe used the dextran sodium sulfate-induced model of colitis in C57BL/6 J wildtype mice treated with either cyclosporine A, voclosporin or solvent control. We employed endoscopy, histochemistry, immunofluorescence, bead-based multiplex immunoassays and flow cytometry to study the therapeutic effect of calcineurin inhibitors in a preventive setting.ResultsAcute colitis was induced by dextran sodium sulfate characterized by weight loss, diarrhea, mucosal erosions and rectal bleeding. Both cyclosporine A and voclosporin strongly ameliorated the course of disease and reduced colitis severity in a similar manner.ConclusionVoclosporin was identified as biologically effective in a preclinical model of colitis and may be a potential therapeutic option in treating acute severe steroid-refractory ulcerative colitis.
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