Megan Levings, PhD
Associate Professor
Department of Surgery, UBC
Canada Research Chair in Transplantation
Michael Smith Foundation Scholar
Associate Member
Department of Microbiology and Immunology, UBC
phone: 604-875-4111 x66742
mlevings(at)interchange.ubc.ca
T Regulatory Cells and Peripheral Tolerance
Research in my laboratory is focused on a novel subset of CD4+ T cells, termed T regulatory (Treg) cells, which control immune homeostasis. Although we know that Treg cells have a fundamental role in regulating immunity to both self and foreign antigens, next to nothing is knows about they arise and function. Current work is focused on determining how Treg cells differ from normal CD4+ T cells at both the biochemical and molecular phenotype, and elucidating their role in transplantation tolerance, cancer and inflammatory bowel disease. A long-term goal is to develop methods to generate Treg cells in vitro for use as a cellular therapy to replace standard immunosuppression in the context of organ transplantation or to restore tolerance in the context of autoimmunity.
- specific projects currently on-going include:
- studying the unique cell-signalling pathways in human and mouse Tregs
- understanding the role of FOXP3 in Tregs and activated T effector cells
- studying the interaction between Tregs and IL-17-producing cells
- studying tissue-derived Tregs from patients with graft versus host disease or inflammatory bowel disease
- the role of dendritic cells in the development of Tregs
- studying the role of Tregs in a mouse model of lung transplantation
Education
PhD - Genetics - University of British Columbia
BSc - Biology - Simon Fraser University
Selected Publications
Allan, S.E., Song-Xiao, G.X., Abraham, T., McMurchy, A.N., and Levings, M.K. Inducible reprogramming of human T cells into T regulatory cells by a conditionally-active form of FOXP3. 2008, Eur. J. Immunol. 38:3282-3289.
Broady, R., Yu, J. and Levings, M.K. Pro-tolerogenic effects of photodynamic therapy with TH9402 on dendritic cells. J. Clin. Apheresis. 2008, 23:82-91.
Passerini, L., Allan, S.E., Battaglia, M., Di Nunzio, S., Alstad, A.N., Levings, MK, Roncarolo, MG, and Bacchetta, R. STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells. Int. Immunol. 2008, 20:421-31.
Allan, S.E., Alstad, A, Merindol, N., Crellin, N.K., Amendola, M., Bacchetta, R., Naldini, L., Roncarolo, MG, Soudeyns, H., and Levings, M.K. In vitro generation of potent and stable human CD4+ T regulatory cells by activation-independent expression of FOXP3. Molecular Therapy. 2008, 16:194-202.
Crellin, N.K., Garcia, R.V., and Levings, M.K. Flow cytometry-based methods for studying signalling in human CD4+CD25+FOXP3+ T regulatory cells. J. of Imm. Methods. 2007, 324:92-104.
Allan, S.E., Crome, S.Q., Crellin, N.K., Passerini, L. Steiner, T.S., Bacchetta, R. Roncarolo, M.G. and Levings, M.K. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int. Immunol. 2007, 19:345 - 354.
Crellin, N.K., Garcia, R.V., and Levings, M.K. Altered activation of AKT is required for the suppressive function of human CD4+CD25+ T regulatory cells. Blood. 2007, 109:2014-2022.
Gianfrani, C., Levings, M.K., Sartirana, C., Mazzarella, G., Zanzi, D., Camarca, A., Iaquinto, G., Giardullo, N., Auricchio, S., Troncone, R., Roncarolo, M.G. Gliadin-specific type 1 regulatory T cells from the intestinal mucosa of treated coeliac patients inhibit pathogenic T cells. J. Immunol. 2006, 177:4178-4186.
Bacchetta, R., Passerini, L., Gambineri, E., Dai, M., Allan, S.E., Sartirana, C., Azzari, C., Ziegler, S.F., Levings, M.K., and Roncarolo, M.G. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J. Clin. Invest. 2006, 116:1713-1722.
Crellin, N., Garcia, R., Allan, S.E., Steiner, T.S., and Levings, M.K. Human CD4+ T cells express TLR5 and its ligand flagellin and enhances the suppressive capacity of and expression of FOXP3 in CD4+CD25+ T regulatory cells. J. Immunol. 2005, 175:8051-8059.
Allan, S.E., Passerini, L., Bacchetta. R., Crellin, N., Dai, M., Orban, P.C., Ziegler, S.F., Roncarolo, M.G., and Levings, M.K. The role of two FOXP3 isoforms in the generation of human CD4+ T regulatory cells. J. Clin. Invest. 2005, 115:3276-3284.
Book chapters and review articles
Broady, R., and Levings, M.K. Graft versus host disease: suppression in statins. Nature Medicine, 2008, 14: 1023-1024.
Locke, N.L., Crellin, N.K. and Levings, M.K. Molecular signalling in T regulatory cells. In Regulatory T cells and Clinical Applications. Ed: Shuiping Jiang. 2008, chapter 8, 135-152.
Himmel, M.E., Hardenberg, G., Piccirillo, C., Steiner, T.S., and Levings, M.K. The Role of T Regulatory Cells and Toll-like Receptors in the Pathogenesis of Human Inflammatory Bowel Disease. Immunology, 2008, 223:391-421.
Allan, SE., Broady, R., Gregori, S., Himmel, ME, Locke, N., Roncarolo, MG, Bacchetta, R. and Levings, MK. CD4+ T regulatory cells: towards therapy for human diseases. Immunological Reviews. 2008, 223:391-421.
Gregori, S., Bacchetta, R., Passerini, L., Levings, M.K. and Roncarolo, M.G. Isolation, expansion, and characterization of human natural and adaptive regulatory T cells. Methods Mol Biol. 2007, 380:83-106.
Levings, M.K., Allan, S.E., d’Hennezel, E., and Piccirillo, C. Functional dynamics of naturally-occurring regulatory T cells in health and autoimmunity. Advances in Immunol. 2006, 92:119-155.
Roncarolo, MG, Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K., and Levings, M.K. IL-10 secreting type 1 regulatory T cells in rodents and humans. Immunological Reviews. 2006, 212:28-50.