MK2 Inhibitors as a Potential Crohn’s Disease Treatment Approach for Regulating MMP Expression, Cleavage of Checkpoint Molecules and T Cell Activity

Eric J. Lebish, Natalie J. Morgan, John F. Valentine, Ellen J. Beswick

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Crohn’s Disease (CD) and Ulcerative Colitis (UC) are the two major forms of inflammatory bowel disease (IBD), which are incurable chronic immune-mediated diseases of the gastrointestinal tract. Both diseases present with chronic inflammation that leads to epithelial barrier dysfunction accompanied by loss of immune tolerance and inflammatory damage to the mucosa of the GI tract. Despite extensive research in the field, some of the mechanisms associated with the pathology in IBD remain elusive. Here, we identified a mechanism by which the MAPK-activated protein kinase 2 (MK2) pathway contributes to disease pathology in CD by regulating the expression of matrix metalloproteinases (MMPs), which cleave checkpoint molecules on immune cells and enhance T cell activity. By utilizing pharmaceuticals targeting MMPs and MK2, we show that the cleavage of checkpoint molecules and enhanced T cell responses may be reduced. The data presented here suggest the potential for MK2 inhibitors as a therapeutic approach for the treatment of CD.

Original languageEnglish
Article number1508
JournalPharmaceuticals
Volume15
Issue number12
DOIs
StatePublished - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

  • Crohn’s Disease
  • Lag3
  • MAPKAPK2
  • MK2
  • PD-L1
  • checkpoint molecules
  • inflammatory bowel disease
  • matrix metalloproteinases (MMPs)

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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