Mucosal Immunology Research
Background
Exploiting our close collaborative links with St. Mark’s Hospital and Institute for Colorectal Diseases we are studying the role of dendritic antigen presenting cells in immune reactions in the human intestine. We study their role in normal intestine, changes evident in patients with inflammatory bowel disease that might underlie the observed inflammatory activity in patients with ulcerative colitis and Crohn’s disease and finally their activity in therapies resulting in resolution of the inflammatory lesions.
Current Research
Probiotic and prebiotic effects on dendritic cells
The major programme of work is to study the impact of different commensal – probiotic bacteria on the functioning of antigen presenting cells. These effects are studied using in vitro models1 as well as following treatment of patients with ulcerative colitis or Crohn's disease 2.
Role of dendritic cells in tissue specific homing
Dendritic cells at mucosal surfaces or in the periphery determine the homing properties of the T cells they stimulate3 promoting migration to mucosal surfaces or peripheral tissues respectively. We have a programme examining the tissue specific properties of the dendritic cells themselves which may underlie their capacity to determine the homing properties of T cells they stimulate.
Leptin receptors and dendritic cells
The adipokine leptin is involved in tissue energy homeostasis but it is also a proinflammatory cytokine. Its activity is determined by its interaction with leptin receptors which include short forms of receptor which are not transmembrane and a longer form of receptor which signals through the JAKSTAT pathway. We are determining the importance of these different receptors and their activation and signalling in dendritic cells. The relative expression of the different forms of leptin receptor and changes in their expression and function in inflammatory bowel diseases are being investigated.
Key Publications
1. Benjamin JL, Hedin CR, Koutsoumpas A, Ng SC, McCarthy NE, Hart AL et al. Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease. Gut 2011; 60:923-929.
2. Lindsay, J. O., K. Whelan, A. J. Stagg, P. Gobin, H. Omar Al-Hassi, N. Rayment, M. A. Kamm, S. C. Knight, and A. Forbes. 2006. The clinical, microbiological and immunological effects of fructo-oligosaccharide in patients with Crohn's disease. Gut 55:348-355.
3. Hart, A. L., A. J. Stagg, and M. A. Kamm. 2003. Use of probiotics in the treatment of inflammatory bowel disease. J.Clin.Gastroenterol. 36:111-119.
4. Stagg, A. J., M. A. Kamm, and S. C. Knight. 2002. Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin. Eur J Immunol 32:1445-1454.
