Scientists explain why Crohn disease is localized to specific regions of the gut

Markus Neurath and fellow researchers at the University of Mainz, Germany, have characterized the interaction between intestinal bacteria and dendritic cells (DCs) that may provide an explanation for the clinical symptoms of Crohn disease that only occur in specific regions of the gut.

The authors used transgenic mice to investigate the expression of the p40 subunit of IL-12 and IL-23. The authors demonstrate that p40 is expressed by a newly identified subset of DCs at greater levels in the lower part of the small intestine when compared to the proximal part of the small intestine or the colon.

Neurath and colleagues demonstrate that p40 production is dependent on the intestinal bacteria as germ-free animals do not exhibit elevated p40 expression in the small intestine.

The data reveal important functional differences between the mucosal immune systems of the small and large bowel in healthy mice and suggest that the high numbers of bacteria in the terminal ileum activate p40 expression. The authors suggest that this pattern of p40 expression may explain the predisposition of the terminal ileum to develop chronic inflammation responses via IL-23 and may therefore provide a molecular reason for the preferential clinical manifestation of Crohn disease in this region of the gut.

In an accompanying commentary, Holm Uhlig and Fiona Powrie from the University of Oxford discuss how intestinal DCs sense bacteria in the gut. They also comment that the IL-12 p40 promoter transgenic mice produced by Neurath and coworkers “will be an excellent tool to study the interaction between particular bacteria and the host immune system and how this influences the localization of the immune response”.

TITLE: Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells

AUTHOR CONTACT:
Markus F. Neurath,
University of Mainz, Mainz, Germany
Phone: 49-6131-172374
Fax: 49-6131-175508
E-mail: neurath@1-med.klinik.uni-mainz.de

ACCOMPANYING COMMENTARY:
Dendritic cells and the intestinal bacterial flora: a role for localized mucosal immune responses

AUTHOR CONTACT:
Fiona Powrie
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
Phone: 44-1865-285494
Fax: 44-1865-275591
E-mail: fiona.powrie@pathology.ox.ac.uk