|Known for||Work on Regulatory T Cells|
|Thesis||Functional analysis of rat T cell subsets|
|Doctoral advisor||Don Mason|
|Academic advisor||Robert L. Coffman|
Fiona Magaret Powrie (born 1963) FRS FMedSci is currently the head of the Kennedy Institute of Rheumatology at the University of Oxford. Formerly she was the inaugural Sidney Truelove Professor of Gastroenterology at the University of Oxford. She is also head of the Experimental Medicine Division of the Nuffield Department of Clinical Medicine.
Regulatory T Cells
Powrie worked with Don Mason at the Sir William Dunn School of Pathology studying the interactions of different subsets of CD4+ T cells in rats. This work identified that CD4+OX22hi (OX22 is CD45RC in rats and the equivalent of CD45RB in mice, both isoforms of CD45) T cells contained pathogenic activity while CD4+OX22lo T cells contained regulatory activity and could prevent the pathogenic activity of CD4+OX22hi T cells These were foundational studies and represented some of the seminal work on regulatory T cells (Treg).
Powrie performed post-doctoral studies with Robert L. Coffman at DNAX in Palo Alto, California. Here, she extended her earlier work in rats to mice and developed the “T cell transfer” model, one of the most prominent models of intestinal inflammation where transfer of CD4+CD45RBhi T cells to Rag deficient or SCID mice led to the development of severe intestinal inflammation and wasting disease. This could be prevented by transfer of CD4+CD45RBlo T cells. Using this model Powrie further identified the pathogenic role played by IFN-γ and TNF-α in intestinal inflammation and the therapeutic potential of IL-10 and highlighted the requirement for TGF-β in the prevention of colitis by the CD4+CD45RBlo regulatory T cell subset Upon returning to the University of Oxford in 1996, first to the Nuffield Department of Surgery and later, the Sir William Dunn School of Pathology, Powrie used the T cell transfer model to identify the suppressive mechanisms used by regulatory T cells to prevent intestinal inflammation including the requirements for CTLA-4 and the capacity of Treg to prevent colitis driven by innate immune cells as well as CD4+ T cells. Focusing on pathogenic mechanisms the Powrie lab. identified the critical role played by the cytokine IL-23 in driving pathology in the intestine
Therapeutic Potential of Tregs
Work from the Powrie lab. identified that Treg could not alone prevent inflammatory bowel disease but could actually cure established inflammation. Furthermore, Powrie was among the first to identify a population of CD4+CD25+ T cells in human peripheral blood that possessed regulatory capacity, confirming these cells as a bona fide T cell subset in humans.
Honors and awards
In 2009, Powrie was appointed as the inaugural Sidney Truelove Professor of Gastroenterology within the Nuffield Department of Clinical Medicine in Oxford. She was elected a Fellow of the Royal Society in 2011, and was awarded the Louis-Jeantet Prize for Medicine in 2012.
- Powrie, Prof. Fiona Margaret | WHO'S WHO & WHO WAS WHO. doi:10.1093/ww/9780199540884.013.255684.
- "Nuffield Department of Clinical Medicine - Prof Fiona Powrie FRS". Ndm.ox.ac.uk. Retrieved 2012-11-15.
- "Keynotes". 2012.the-embo-meeting.org. Retrieved 2012-11-15.
- "A delicate balance: Investigating intestinal inflammation « Wellcome Trust Blog". Wellcometrust.wordpress.com. 2012-01-31. Retrieved 2012-11-15.
- Saouid A, Seddon B, Heath V, Fowell D, Mason D (1996). "The physiological role of regulatory T cells in the prevention of autoimmunity: the function of the thymus in the generation of the regulatory T cell subset". Immunological Reviews. 149: 195–216. doi:10.1111/j.1600-065x.1996.tb00905.x. PMID 9005215.
- Powrie F, Mason D (1990). "OX-22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22low subset". Journal of Experimental Medicine. 172 (6): 1701–8. doi:10.1084/jem.172.6.1701. PMC 2188779
. PMID 2258700.
- Powrie F, Leach MW, Mauze S, Caddle LB, Coffman RL (1993). "Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice". International Immunology. 5 (11): 1461–71. doi:10.1093/intimm/5.11.1461. PMID 7903159.
- Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL (1994). "Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells". Immunity. 1 (7): 553–62. doi:10.1016/1074-7613(94)90045-0. PMID 7600284.
- Powrie F, Carlino J, Leach MW, Mauze S, Coffman RL (1996). "A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells". Journal of Experimental Medicine. 183 (6): 2669–74. doi:10.1084/jem.183.6.2669. PMC 2192626
. PMID 8676088.
- Read S, Malmstrom V, Powrie F (2000). "Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation". Journal of Experimental Medicine. 192 (2): 295–302. doi:10.1084/jem.192.2.295. PMC 2193261
. PMID 10899916.
- Maloy KJ, Salaun L, Cahill R, Dougan G, Saunders NJ, Powrie F (2003). "CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms". Journal of Experimental Medicine. 197 (1): 111–9. doi:10.1084/jem.20021345. PMC 2193798
. PMID 12515818.
- Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ (2006). "Interleukin-23 drives innate and T cell-mediated intestinal inflammation". Journal of Experimental Medicine. 203 (11): 2473–83. doi:10.1084/jem.20061099. PMC 2118132
. PMID 17030949.
- Mottet C, Uhlig HH, Powrie F (2003). "Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells". Journal of Immunology. 170 (8): 3939–43. doi:10.4049/jimmunol.170.8.3939. PMID 12682220.
- Stephens LA, Mottet C, Mason D, Powrie F (2001). "Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro". European Journal of Immunology. 31 (4): 1247–54. doi:10.1002/1521-4141(200104)31:4<1247::AID-IMMU1247>3.0.CO;2-M. PMID 11298351.
- "Professor Fiona Margaret Powrie FRS". Royal Society. Retrieved 2012-11-15.
- "2012 Louis-Jeantet Prize for Medicine". Eurekalert.org. Retrieved 2012-11-15.