University of Oxford           
7. Fiona Powrie, professor, group leader
Kevin Maloy, Ph.D., senior staff member
     Sir William Dunn School of Pathology
     University of Oxford
     South Parks Road
     Oxford OX1 3RE
     United Kingdom
     Fax: (01865) 275591
     Emai address:

The group led by Dr. Powrie is part of the Sir William Dunn School of Pathology at the University of Oxford. The Dunn School has an extensive research program covering a wide range of fields such as immunology, cell biology, bacteriology, virology and molecular biology. The excellent core infrastructure means that all of the technical facilities required to conduct the proposed experiments are already present on site. These include SPF animal facilities fitted with Thoren rack systems that permit individual cage ventilation, high speed FACS, bioimaging suites, microarray analyses and microbiological culture suites. The gastrointestinal tract is one of the major sites of immunological challenge to the host immune system, where the host must effectively respond to invading pathogenic agents, whilst remaining tolerant of innocuous dietary antigens and commensal flora. The primary research focus of the group is on the dissection of factors that govern T cell responsiveness or tolerance in the intestine and identification of immune regulatory mechanisms, especially regulatory T cells and their cytokines. Around 10 years ago, Dr Powrie developed a murine model of inflammatory bowel disease, based on the transfer of CD4+ T cells into immune deficient recipients. Subsequent analyses of this model demonstrated that intestinal inflammation was a consequence of a T cell-mediated inflammatory response against the commensal bacterial flora. More recently, we developed an additional model of intestinal inflammation that is driven by infection with the murine bacterial pathogen, Helicobacter hepaticus. In the latter case, inflammation is T cell-independent and is due to excessive activation of innate immune cells. In both kinds of immune mediated intestinal pathology, pro-inflammatory cytokines (IL-12 and IFN-g) play a key role in driving intestinal inflammation, whereas anti-inflammatory cytokines (IL-10 and TGF-ß) are essential for inhibition of disease. These studies were also instrumental in identifying a subset of normal CD4+ T cells designated as regulatory T cells, that function to suppress immune pathology in vivo. Together, these models provide powerful tools with which to dissect the roles of defined leukocyte populations and defined cytokines in both the induction and inhibition of intestinal inflammation. As such, the Powrie group will provide the network with expertise and training in the analyses of potent immune pathological reactions in vivo. The results yielded by combining the conditional cytokine and cytokine receptor KO mice to be generated in this project with these inflammatory bowel disease models, should provide important information for the design of therapeutic agents for the treatment of autoimmune and inflammatory diseases.

Appointed research fellows

Experienced researcher: Sofia Buonocore, Italy
Appointed on the IMDEMI project from 1-12-2005 to 30-11-2007

Early stage researcher:
Philip Ahern, Ireland
Appointed on the IMDEMI project from 1-10-2005 to 30-9-2008

Early stage researcher:
Eva Kiss, Hungary
Appointed on the IMDEMI project from 1-3-2009 to 31-5-2009

Publications originating from the IMDEMI project

Ahern PP, Izcue A, Maloy KJ, Powrie F. The interleukin-23 axis in intestinal inflammation. Immunol Rev 226: 147-159, 2008. (PDF)

Izcue A, Hue S, Buonocore S, Arancibia-Cárcamo CV, Ahern PP, Iwakura Y, Maloy KJ, Powrie F. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity 28: 559-570, 2008. (PDF)

Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med 203: 2473- 2483, 2006. (PDF)

Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce-Shaikh B, Stepankova R, Robinson N, Buonocore S, Tlaskalova-Hogenova H, Cua DJ, Powrie F. Differential activity of IL-12 and IL- 23 in mucosal and systemic innate immune pathology. Immunity 2: 309-318, 2006. (PDF)

Publications Fiona Powrie (link to PubMed)

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