Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin

Ashcroft, A. J., Cruickshank, S. M., Croucher, P. I., Perry, M. J., Rollinson, S., Lippitt, J. M., Child, J. A., Dunstan, C., Felsburg, P. J., Morgan, G. J. and Carding, S. R. (2003) Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin. Immunity, 19 (6). pp. 849-861. ISSN 1097-4180

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Abstract

Autoimmune associated bone disease and intestinal inflammation are closely linked with deregulation and hyperactivation of autoreactive CD4 T cells. How these T cells are activated and mediate disease is not clear. Here we show that in the Interleukin 2-deficient mouse model of autoimmunity spontaneous osteopenia and colitis are caused by increased production of the ligand for receptor activator of NFκB (RANKL). RANKL acting via its receptor, receptor activator of NFκB (RANK), increases bone turnover and promotes intestinal dendritic cell (DC) survival in vivo. Modulation of RANKL-RANK interactions with exogenous recombinant osteoprotegerin (Fc-OPG) reverses skeletal abnormalities and reduces colitis by decreasing colonic DC numbers. This study identifies a common causal link between bone disease and intestinal inflammation and establishes the importance of DC in mediating colonic inflammation in vivo.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User:	Rhiannon Harvey
Date Deposited:	14 Jul 2011 10:50
Last Modified:	28 Mar 2025 04:29
URI:	https://ueaeprints.uea.ac.uk/id/eprint/33712
DOI:	10.1016/S1074-7613(03)00326-1

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