Lesley E. Smythies, Ph.D.
Dr. Smythies earned her B.Sc. (Hons), A.K.C. at Kings College, London University, England and her Ph.D. at Wye College, London University. She then did postdoctoral fellowships in the Department of Physiology and Biophysics at UAB and the Department of Biology at the University of York, England. She returned to UAB and joined the Department of Medicine as a Research Associate in 1998, advancing to Research Assistant Professor in 2002 and Associate Professor in 2006.
Dr. Smythies' research focus is human mucosal immunology, in particular the immunobiology of mucosal antigen presenting cells (macrophages and dendritic cells), and the host immunological response to parasite and bacterial pathogens. She focused originally on pulmonary immunology, helping to define the T cell cytokine regulation of the host response to Schistosoma mansoni. She went on to elucidate the role of interferon- regulation of nitric oxide production in host defense against African trypanosome infections. Recently, she turned her investigative attention to the mucosal immune response to Helicobacter pylori. Using a mouse model of the infection that she developed, she has shown that H. pylori inflammation is Th1-mediated and with colleagues is exploring the protective T regulatory cell response of children versus adults to infection with H. pylori. Recent studies in her laboratory have focused on intestinal extracellular (stromal) immune matrix regulation of primary human mucosal macrophages and dendritic cells in mucosal infections and in IBD. In highly novel studies, she has shown that the lamina propria stroma (including intestinal fibroblasts) plays a critical role in monocyte differentiation into non-inflammatory, but powerfully bactericidal, intestinal macrophages and she has elucidated the defective signal transduction pathway(s) underlying the down-regulated inflammatory response of intestinal macrophages to bacterial antigens. New studies elucidate how the lamina propria stroma also conditions intestinal dendritic cell and mucosal T cell function. Dr Smythies was also the first to identify, isolate and characterize human gastric dendritic cells and to show that the microenvironment of the gastric mucosa conditions and regulates gastric dendritic cell responses to H. pylori infection which, in turn, drive responsive CD4 T cell proliferation and IFN- release against H. pylori.
1. Smythies, L.E., Waites, K.B., Lindsey, J.R., Harris, P.R., Ghiara, P., and Smith, P.D. Helicobacter pylori–induced mucosal inflammation is Th1-mediated and exacerbated in interleukin-4, but not interferon-gamma, gene-deficient mice. J. Immunol. 165:1022-1029, 2000.
2. Smythies, L.E., Sellers, M., Clements, R.H., Mosteller-Barnum, M., Meng, G., Benjamin, W.H., Orenstein, J.M. and Smith, P.D. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J. Clin. Invest. 115:66-75, 2005.
3. L.E. Smythies, L. Wahl, S.M. Wahl and P.D. Smith. Isolation of monocytes and intestinal macrophages from human peripheral blood and tissue. Current Protocols in Immunology (2006) 7.6B.1-9.
4. P.D. Smith, C. Ochsenbauer-Jambor and L.E. Smythies. Intestinal macrophages: unique effector cells of the innate immune system. Immunological Review (2006) 149-159.
5. P.R. Harris, S. Wright, C. Serrano, F. Riera, I. Duarte, J.Torres, A. Peña, A. Rollán, P. Viviani, E. Guiraldes, J. Schmitz, R.G. Lorenz, L. Novak, L.E. Smythies and P.D. Smith. Helicobacter pylori gastritis in children is associated with a T regulatory cell response. Gastroenterology (2008) 134:491-499.
6. L.E. Smythies, R. Shen, D. Bimczok, L. Novak, R.H. Clements, E.R. Drelichman, D.E. Eckhoff, P. Bouchard, M.D. George, S. Dandekar and P.D. Smith. Inflammation anergy in human intestinal macrophages is due to Smad-induced IκBα expression and NF-κB Inactivation. Journal of Biological Chemistry (2010) 285:19593-19604. PMCID: PMC2885238.
7. D. Bimczok, R.H. Clements, K.B. Waites, L. Novak, D.E. Eckhoff, P.J. Mannon, P.D. Smith and L.E. Smythies. Human primary gastric dendritic cells induce a Th1 response to H. pylori. Mucosal Immunology (2010) 3:260-269. PMCID: PMC3683837.
8. R. Shen, L.E. Smythies (Joint first authors), R.H. Clements, L. Novak and P.D. Smith. Dendritic cells transmit HIV-1 through human small intestinal mucosa. Journal of Leukocyte Biology (2010) 87:663-670. PMCID: PMC2858307.
9. K.R. Huff, L.N. Akhtar, A.L. Fox, J.A. Cannon, P.D. Smith and L.E. Smythies. Extracellular matrix-associated cytokines regulate CD4+ effector T-cell responses in the human intestinal mucosa. Mucosal Immunology (2011) doi: 10.1038/mi.2010.86. PMCID: PMC3118864
10. D. Bimczok, J.M. Grams, R.D. Stahl, K.B. Waites, L.E. Smythies, and P.D. Smith. Stromal Regulation of Human Gastric Dendritic Cells Restricts the Th1 Response to H. pylori. Gastroenterology (2011) 141:929-938. PMCID: PMC3163821.