Authors have contributed equally.
Inflamed gut mucosa: downstream of interleukin-10
Article first published online: 1 JUN 2011
© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 42, Issue 1, pages 95–109, January 2012
How to Cite
Paul, G., Khare, V. and Gasche, C. (2012), Inflamed gut mucosa: downstream of interleukin-10. European Journal of Clinical Investigation, 42: 95–109. doi: 10.1111/j.1365-2362.2011.02552.x
- Issue published online: 7 DEC 2011
- Article first published online: 1 JUN 2011
- Received 24 March 2011; accepted 4 May 2011
- Inflammatory bowel disease;
- interleukin-10 receptor
Eur J Clin Invest 2012; 42 (1): 95–109
Background Interleukin-10 is a pleiotropic cytokine, whose main function is limitation and ultimately termination of immune responses. This is especially true for environmental interfaces such as the gastrointestinal tract. IL-10 acts as a key mediator for maintaining gut homeostasis. IL-10 knockout mice are well established as a genetic model for inflammatory bowel disease (IBD), and sequence variants in the IL-10 locus contribute to ulcerative colitis (UC).
Design This review covers the significance of IL-10 signalling in the intestinal immune response both in health and disease. It explains the biological role of IL-10, its deregulation in IBD and its contribution to intestinal inflammation via endoplasmic reticulum stress response.
Results Many IBD susceptibility genes have been discovered in the past years, linking fundamental biological systems, like innate and adaptive immunity, stress responses, autophagy and mucosal barrier to the pathogenesis of Crohn’s disease (CD) and UC. IL-10 has long been known for its substantial role in regulating gut immunity, but its contribution to IBD was somewhat elusive. A recent study identified mutations in either IL-10 receptor subunits that are associated with early-onset enterocolitis, a severe phenotype of IBD. Other than genetic variants of IL-10 receptors, IL-10 and STAT3 genes are also associated with IBD, emphasizing the involvement of the IL-10 signalling cascade in the pathogenesis of CD and UC.
Conclusions The discovery of inherited deregulations in the IL-10 signalling cascade is not only considered the missing link between IL-10 and intestinal homeostasis, but also demonstrates how findings made in animal models help explaining human disease.