Regulation of gut immune response
19 February 2008
The cells in the intestinal wall have a tricky balancing act to perform. They must generate an immune response to defend the body against pathogens in the gut but must not react to dietary antigens or the symbiotic microbes that have made it their home. Research led by Professor Fiona Powrie, Wellcome Trust Senior Research Fellow at the University of Oxford, is piecing together the complex web of interactions that maintain this delicate balance.
It is becoming increasingly clear that the gut's immune mechanisms play a key role in our defence - but also contribute to common medical complaints. Around 1 in 1000 people in developed countries endures inflammatory bowel disease (IBD), where an overactive immune system ends up damaging the body's own tissues.
A possible answer to the miseries of IBD may lie with regulatory T cells: immune cells exciting great interest because of the ability to turn off unwanted immune responses. Professor Powrie's research has revealed much about how these cells operate, both in normal health and in inflammatory conditions such as IBD.
Of particular interest has been the discovery that, unlike most tissues, the gut does not depend only on regulatory T cells from the thymus - it produces its own. This production is dependent on a classical regulatory T cell stimulus, TGF-β, and the vitamin A metabolite retinoic acid. It also appears that regulatory T cells occupy a distinct location in the gut tissue.
Professor Powrie's group has also identified factors that may tip the intestinal balance towards over-reaction. The cytokine IL-23, for example, seems to be specifically involved in promoting inflammatory reactions in the gut - and is thus an exciting new target for IBD therapies.
Further reading
- Coombes JL et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 2007;204(8):1757-64.
- Uhlig HH et al. Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis. J Immunol 2007;177(9):5852-60.
- Uhlig HH et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 2006;25(2):309-18.
- Hue S et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med 2006;203(11):2473-83.
- Kullberg MC et al. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J Exp Med. 2006 Oct 30;203(11):2485-94.