Nutrition and Immunity Research
Background
Our basic studies and those in patients with inflammatory bowel disease are ultimately aimed at producing individualised, evidence-based, dietary therapy for patients with Crohn’s disease or ulcerative colitis.
Mounting an immune response requires an energy resource. Dietary fats and sugars provide basic resources but availability of these materials to cells of the immune system and their uptake and metabolism in these cells may not only fuel immune activity but also cause immunomodulatory effects. Such immunomodulatory effects acting via regulating the functions of the key antigen presenting cells, dendritic cells (DC), are studied in our department.
Current Research
Interaction of fatty acids and DC
DC can take up excessive quantities of fatty acids. Under different conditions of antigenic exposure DC contain large lipid bodies of either saturated or unsaturated fatty acids1. Uptake and metabolism of fatty acids and their functional consequences are therefore a major interest in our laboratory.
Fat around human lymph nodes and in the omentum is specialised to interact cells of the immune system; the fat is high in polyunsaturated fatty acids, contains high numbers of dendritic antigen presenting cells and produces adipokines that interact with cells of the immune system. A major feature of Crohn’s disease is early hypertrophy of mesenteric adipose tissue.
Changes in these features occur in the mesentery in Crohn’s disease2-4. Characterising these changes and their impact on immune function is underway.
Advanced glycation end products
Excessive glucose metabolism raises concentrations of the reactive dicarbonyal methylglyoxal (MG). MG can alter target protein molecules by forming advanced glycation end products which are post translational modifications known to perpetuate vascular and neuronal injuries particularly as long term complications of diabetes. Our recent evidence suggests that MG may modulate immune function particularly via effects on dendritic antigen presenting cells5. We are studying the nature and relevance of such changes to the functioning of cells of the immune system in vitro and are interested in identifying their relevance to changes in immune system in vivo6-7.
Key publications
1. Ng SC, Plamondon S, Kamm MA, et al. Immunosuppressive effects via human intestinal dendritic cells of probiotic bacteria and steroids in the treatment of acute ulcerative colitis. Inflamm Bowel Dis 2010;16:1286-98.
2. Herber DL, Cao W, Nefedova Y, et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nature Med 2010;16:880-U57.
3. Price CL, Knight SC. Methylglyoxal: possible link between hyperglycaemia and immune suppression? Trends Endocrinol Metab 2009; 20(7):312-317
4. Knight, S. C. 2008. Specialized perinodal fat fuels and fashions immunity. Immunity 28:135-138.
5. Price, C.L. and Knight, S.C. 2007. Advanced glycation: a novel outlook on atherosclerosis. Current Pharmaceutical Design 13 (36), 3681-3687
6. Bedford, P. A., V. Todorovic, E. D. A. Westcott, A. C. J. Windsor, N. R. English, H. O. Al Hassi, K. S. Raju, S. Mills, and S. C. Knight. 2006. Adipose tissue of human omentum is a major source of dendritic cells, which lose MHC Class II and stimulatory function in Crohn's disease. J.Leuk.Biol. 80:546-554.
7. Maroof A., English N.R., Bedford P.A., Gabrilovich D.I., & Knight S.C. (2005) Developing dendritic cells become 'lacy' cells packed with fat and glycogen. Immunology 115, 473-483.
8. Westcott E.D.A., Windsor A.C.J., Mattacks C.A., Pond C.M., & Knight S.C. (2005) Fatty acid compositions of lipids in mesenteric adipose tissue and lymphoid cells in patients with and without Crohn's disease and their therapeutic implications. Inflamm.Bowel.Dis. 11, 820-826.
9. Price, C. L., P. S. Sharp, M. E. North, S. Rainbow, and S. C. Knight. 2004. Advanced glycation end-product modulates the maturation and function of peripheral blood dendritic cells. Diabetes 53:1452-1458
