The role of dendritic cells in regulating mucosal immunity and tolerance

Mowat, A.M., Donachie, A.M., Parker, L.A., Robson, N.C., Beacock-Sharp, H., McIntyre, L.J., Millington, O. and Chirdo, F. (2003) The role of dendritic cells in regulating mucosal immunity and tolerance. Novartis Foundation Symposium, 252, pp. 291-302. (PMID:14609226)

Abstract

The intestinal immune system discriminates between invasive pathogens and antigens that are harmless, such as food proteins and commensal bacteria. The latter groups of antigens normally induce tolerance and a breakdown in this homeostatic process can lead to diseases such as coeliac disease or Crohn's disease. The nature ofthe intestinal immune response depends on how antigen is presented to CD4+ T cells by dendritic cells (DCs). Both oral tolerance and priming are influenced by the numbers and activation status of DCs in the gut and its draining lymphoid tissues, and our current work indicates that dietary proteins are taken up preferentially by DCs in the lamina propria of the small intestine. These then migrate to interact with antigen-specific CD4+ T cells in the mesenteric lymph node. In vivo and in vitro studies using purified lamina propria DCs suggest these may play a unique role in the regulation of intestinal immune responses. We propose that local DCs are the gatekeepers of the mucosal immune system, inducing tolerance under physiological conditions, but being sufficiently responsive to inflammatory stimuli to allow T cell priming and protective immunity when necessary. In addition, we will discuss evidence that adjuvant vectors such as ISCOMS may be effective mucosal vaccines due to an ability to activate intestinal DCs.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Robson, Dr Neil and Mowat, Professor Allan and Donachie, Ms Anne Marie
• Authors: Mowat, A.M., Donachie, A.M., Parker, L.A., Robson, N.C., Beacock-Sharp, H., McIntyre, L.J., Millington, O., and Chirdo, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Novartis Foundation Symposium
• Publisher: John Wiley & Sons Ltd.
• ISSN: 1528-2511
• ISSN (Online): 1935-4657