The Bland group focusses on three main areas of mucosal immunobiology, both within MIVAC and also within the University of Bristol, UK:
1. Chronic mucosal inflammation
Because the intestinal barrier is relatively friable, we all probably encounter frequent local erosion of this barrier and mild, localised, acute inflammation which resolves using normal healing mechanisms. In some individuals, however, the normal healing process does not initiate and the inflammation becomes chronic – inflammatory bowel disease. There are many potential underlying mechanisms: defects in the epithelial barrier; defects in innate immune recognition events; defects in wound healing responses. Using in vitro and in vivo model systems and clinical material, the group is investigating interactions between commensal bacteria and epithelial tight junction remodelling; mucosal dendritic cell – commensal bacteria interactions; and the role of the mucosal fibroblast in regulating the acute-chronic switch. All of these studies involve analysis of signal transduction pathways.
2. Antigen handling at mucosal surfaces
Antigen access to the mucosal immune system across the barrier is quantitatively and qualitatively regulated at two critical checkpoints: the epithelium and the associated dendritic cells. The group is actively involved in subcellular analysis of epithelial mechanisms for processing different types of antigens – food and microbial – which generate tolerogenic and active immune responses. Paracellular and transcellular pathways are being investigated, again mostly by analysis of signal transduction. Mucosal dendritic cells are complex. We are particularly interested in those directly receiving antigen via the absorptive epithelium. Because of our parallel interests in mucosal inflammation, we concentrate on the regulation of antigen handling in the large intestine – which is the site of colonisation of most commensal organisms, and where most inflammatory pathology occurs.
3. Perinatal immune development
Although it is known that environmental events very early in life influence the adult immune response, very little is known about the way in which the developing mucosal immune system of the neonate interacts with food and microbes, or how these antigens influence immune development. We are carrying out analyses in human and model systems to understand those parameters which define the immune repertoire in neonates and regulate subsequent adult immune responses.
Williams AM, Probert CSJ, Stepankova R, Tlaskalova, H, Phillips A and Bland PW. (2006) Effects of microflora on the neonatal development of gut mucosal T cells and myeloid cells in the mouse. Immunology, Published online Sept 2006
MProbert CSJ, Williams AM, Stepankova R, Tlaskalova H, Phillips A, and Bland PW. (2006) Ontogeny of the oligoclonal repertoire of ab T cell receptor T cells in the murine intestine: influence of weaning and bacteria. Dev Cell Immunol, in press.
Tlaskalova-Hogenova H, Tuckova L, Stepankova R, Hudcovic T, Palova-Jelinkova L, Kozakova H, Rossmann P, Sanchez D, Cinova J, Hrincir T, Kverka M, Frolova L, Uhlig H, Powrie F and Bland PW. (2005) Involvement of innate immunity in the development of inflammatory and autoimmune diseases. Ann NY Acad Sci 1051, 787-798.
Bjursten M, Bland PW, Willen R and Hornquist E. (2005) Long term treatment with anti-α4 integrin antibodies aggravates colitis in Gαi2-deficient mice. Eur J Immunol, 35, 2269-2273.
Whiting CV, Bland PW and Tarlton JF. (2005) Dietary n-3 polyunsaturated fatty acids reduce disease and colonic proinflammatory cytokines in a mouse model of colitis. Inflamm Bowel Dis, 11, 340-349.
Williams AM, Bland PW, Phillips AC, Turner S, Brooklyn T, Shaya G, Spicer RD, and Probert CSJ. (2004) Intestinal a/bT cells differentiate and rearrange antigen receptor genes in situ in the human infant. J Immunol 173, 7190-7199.