Mechanisms of mucosal healing: treating inflammatory bowel disease without immunosuppression?
Top Cited Papers
- 19 April 2022
- journal article
- review article
- Published by Springer Nature in Nature Reviews Gastroenterology & Hepatology
- Vol. 19 (8) , 493-507
Abstract
Almost all currently available treatments for inflammatory bowel disease (IBD) act by inhibiting inflammation, often blocking specific inflammatory molecules. However, given the infectious and neoplastic disease burden associated with chronic immunosuppressive therapy, the goal of attaining mucosal healing without immunosuppression is attractive. The absence of treatments that directly promote mucosal healing and regeneration in IBD could be linked to the lack of understanding of the underlying pathways. The range of potential strategies to achieve mucosal healing is diverse. However, the targeting of regenerative mechanisms has not yet been achieved for IBD. Stem cells provide hope as a regenerative treatment and are used in limited clinical situations. Growth factors are available for the treatment of short bowel syndrome but have not yet been applied in IBD. The therapeutic application of organoid culture and stem cell therapy to generate new intestinal tissue could provide a novel mechanism to restore barrier function in IBD. Furthermore, blocking key effectors of barrier dysfunction (such as MLCK or damage-associated molecular pattern molecules) has shown promise in experimental IBD. Here, we review the diversity of molecular targets available to directly promote mucosal healing, experimental models to identify new potential pathways and some of the anticipated potential therapies for IBD.Keywords
This publication has 226 references indexed in Scilit:
- IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestineNature, 2012
- Interleukin 23 Production by Intestinal CD103+CD11b+ Dendritic Cells in Response to Bacterial Flagellin Enhances Mucosal Innate Immune DefenseImmunity, 2012
- Enterocyte STAT5 promotes mucosal wound healing via suppression of myosin light chain kinase‐mediated loss of barrier function and inflammationEMBO Molecular Medicine, 2012
- The Aryl Hydrocarbon Receptor Regulates Gut Immunity through Modulation of Innate Lymphoid CellsImmunity, 2012
- The light and dark sides of intestinal intraepithelial lymphocytesNature Reviews Immunology, 2011
- Genome-wide association identifies multiple ulcerative colitis susceptibility lociNature Genetics, 2010
- IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated CancerCancer Cell, 2009
- MAGI2 genetic variation and inflammatory bowel diseaseInflammatory Bowel Diseases, 2009
- Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformationLaboratory Investigation, 2008
- Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epitheliaLaboratory Investigation, 2007