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SRI Profiles

Philippe Poussier, MD

Senior Scientist

Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room A3 38
Toronto, ON
M4N 3M5

Phone: 416-480-6136
Fax: 416-480-4375

Administrative Assistant: Sue Santillo
Phone: 416-480-6100, ext. 3914
Email: sue.santillo@sunnybrook.ca

Education:

  • MD, 1973, Cochin Faculty of Medicine, Paris University, France

Appointments and Affiliations:

Research Focus:

  • Pathogenesis of type 1 diabetes
  • Inflammatory bowel disease

Research Summary:

The aetiology of autoimmune type 1A diabetes (T1D) remains unknown. A powerful approach to gain insights into the pathogenesis of the human disease has been to study inbred laboratory animals that spontaneously develop T1D. To facilitate the identification of genetics factors contributing to the development of T1D in BB rats, and to further our understanding of the immune mechanisms responsible for the destruction of â cells in these animals, we have developed several congenic lines of rats in which isolated loci convey powerful effects on specific steps in T1D pathogenesis. One of our research projects is based on the use of these congenic lines that exhibit differential susceptibility to T1D. Our overall objectives are to identify novel T1D susceptibility genes, and to characterize the mechanisms through which these genes contribute to disease development. This research project is supported by Genome Canada and the Canadian Institutes of Health Research.

Inflammatory bowel diseases (IBD) result from a dysregulated immune response to environmental antigens, including the endogenous microflora, in genetically susceptible individuals. We have demonstrated that the development of intestinal intraepithelial T lymphocytes (iIEL) is impaired in IBD-prone IL-2/IL-2R-/- mice. This led us to directly assess the capacity of iIEL subsets to regulate the development of colitis secondary to transfer of splenic CD4+CD45RBhi T cells into SCID mice. While prior reconstitution of SCID recipients with TcRáâ+,CD4,-8á+â- iIEL prevented disease, and did so in an IL-10 dependent fashion, reconstitution with other iIEL subsets did not prevent colitis.

The X-linked Wiskott-Aldrich syndrome is associated with a high incidence of IBD. The defective protein, (WASP), is expressed exclusively in hemopoietic cells. We have observed an impaired development of iIEL, independent of genetic background, but profoundly influenced by environmental factors in WASP-/- mice. Specifically, TcRáâ+,CD4-8á+â- iIEL are absent in WASP-/- mice only when these animals are reared in a conventional environment (CE). Further, WASP-/- 129Sv mice develop severe colitis in a CE, but not in an SPF environment. In contrast, WASP-/- C57BL/6 mice remain IBD-free in both circumstances. Our hypothesis is that the development of IBD in WASP-/- mice maintained in a CE requires a dysregulation of iIEL development and/or function as well as genetic factors that regulate the immune response of mucosal T cells to microbial antigens. Our specific aims are to characterize the role of IL-10 in protection from colitis afforded by CD4-dá+â-, TcRáâ+ iIEL, to determine whether, and how restoring a normal complement of CD4-8á+â-, TcRáâ+ IEL in WASp-deficient 129Sv mice prevents the development of IBD in a CE, and to map the loci containing the genes responsible for the differential susceptibility of WASp-deficient 129Sv and C57BL/6 mice to spontaneous IBD in a CE. This research project is supported by the Canadian Institutes of Health Research.

Selected Publications:

See current publications list at PubMed.

    1. Ramanathan, S., Norwich, K., and Poussier, P. Antigen activation rescues recent thymic emigrants from programmed cell death in the BB rat. J. Immunol. 160: 5757-5764, 1998.
    2. Ramanathan, S., and Poussier, P. T cell reconstitution of BB/W rats after the initiation of insulitis precipitates the onset of diabetes. J. Immunol. 162: 5134-5142, 1999.
    3. Ramanathan, S., Marandi, L., and Poussier, P. Evidence for extrathymic origin of intestinal TcR T cells in normal rats and for an impairment of this differentiation pathway in BB rats. J. Immunol. 168: 2182-2187, 2002.
    4. Ramanathan, S., Bihoreau, M-T., Paterson, A. D., Marandi, L., Gauguier D., and Poussier, P. Thymectomy- and radiation- induced type 1 diabetes in non-lymphopenic BB rats. Diabetes 51: 2975-2981, 2002.
    5. Ilangumaran, S., Ramanathan, S., La Rose, J., Poussier, P., and Rottapel, R. Suppressor of cytokine signaling 1 regulates IL-15 receptor signaling in CD8+CD44hi memory T lymphocytes. J. Immunol. 171: 2435-2445, 2003.

      Related News and Stories:

      • Gut reaction: immune response to intestinal bugs linked to diabetes risk: study (March 28, 2019)
      • Science, Spontaneously: Immunologist at SRI identifies two animal genes that predispose people for developing Type 1 diabetes (July 7, 2006)

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