Gudrun Philomena Fiona Debes
Assistant Professor of Microbiology and Immunology
317 Hill Pavilion,
380 South University Avenue
Philadelphia, PA 19104
Office: (215) 573-9167
Fax: (215) 746-2295Email:firstname.lastname@example.org
DVM (Immunology/Veterinary Medicine) Free University Berlin and Humboldt University (Berlin, Germany), 2002
Description of Research Expertise
Effector and memory lymphocytes, unlike naïve lymphocytes, can efficiently enter extralymphoid tissues as well as sites of inflammation and infection. Subsequently, lymphocytes enter the afferent lymph to reach draining lymph nodes. After a short time period of residency, lymphocytes exit the lymph node via the efferent lymph, which brings them back into the blood. This dynamic process of lymphocyte recirculation, which is tightly regulated at each step, is essential for immune surveillance and efficient defense against pathogens, but it can also contribute to the development of inflammatory diseases.
My laboratory seeks to understand the regulation of lymphocyte recirculation as well as the microenvironmental localization of effector and memory lymphocytes within extralymphoid tissues. Currently, we are interested in defining the molecules involved in lymphocyte exit from peripheral tissues and its significance to protective as well pathologic immune responses in the tissue. We employ modern approaches of multi-color flow cytometry, molecular biology, gene expression profiling, histology, and in vivo models. We complement genetic and adoptive transfer mouse models with a classic model of lymph cannulation in the sheep that allows us to analyze cell compartments that are inaccessible in rodents because of their small size.
Understanding the mechanisms involved in cellular localization and recirculation will provide tools to therapeutically manipulate protective as well as inflammatory immune responses.
* Mechanisms of lymphocyte exit from tissues during inflammation and infection. Significance to pathogen clearance and inflammation.
* Control of lymphocyte retention in extralymphoid tissues and its relevance to long-term protection against influenza virus infection.
* Regulation of T cell egress from inflamed skin employing models of adjuvant-induced skin granulomas as well as Leishmania major infection (the latter in collaboration with Dr. Philip Scott).
* Recirculation strategies of B and T lymphocyte subsets.
Diehl, M.C and G.F. Debes: CCL8 and skin T cells – an allergic attraction. Nature Immunology 12: 111-112, 2010.
Brown, M.N., S.R. Fintushel, M.H. Lee, S. Jennrich, S.A. Geherin, J.B. Hay, E.C. Butcher, and G.F. Debes: Chemoattractant receptors and lymphocyte egress from extralymphoid tissue: changing requirements during the course of inflammation. The Journal of Immunology 185: 4873-4882, 2010.
Knieke, K., H. Hoff, F. Maszyna, P. Kolar, A. Schrage, A. Hamann, G.F. Debes, and M.C. Brunner-Weinzierl: CD152 (CTLA-4) determines CD4 T cell migration in vitro and in vivo PLoS One 4: e5702, 2009.
Debes, G.F. and S.L. Reiner: Helping and harming have something in common Nature Immunology 10: 138, 2009.
Sigmundsdottir, H., J. Pan, G.F. Debes, C. Alt, A. Habtezion, D. Soler, and E.C. Butcher: Dendritic cells metabolize sunlight-induced Vitamin D3 to program T cell attraction to the epidermal chemokine CCL27 Nature Immunology 8: 285, 2007.
Debes, G.F., M.E. Dahl, A.J. Mahiny, K. Bonhagen, D.J. Campbell, K. Siegmund, K.J. Erb, D.B. Lewis, T. Kamradt, and A. Hamann: Chemotactic responses of IL-4-, IL-10- and IFN-?-producing CD4+ T cells depend on tissue origin and microbial stimulus The Journal of Immunology 176: 557, 2006.
Debes, G.F., C.N. Arnold, A.J. Young, S. Krautwald, M. Lipp, J.B. Hay, and E.C. Butcher.: Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues Nature Immunology 6: 889, 2005.
Kretschmer, U., K. Bonhagen, G.F. Debes, H. Mittrücker, K. J. Erb, O. Liesenfeld, D. Zaiss, T. Kamradt, U. Syrbe, and A. Hamann: Expression of selectin ligands on murine effector- and IL-10 producing CD4+ T cells from non-infected and infected tissues European Journal of Immunology 34: 3070, 2004.
Huehn, J., K. Siegmund, J.C. Lehmann, C. Siewert, U. Haubold, M. Feuerer, G.F. Debes, J. Lauber, O. Frey, G.K. Przybylski, U. Niesner, M. De La Rosa, C.A. Schmidt, R. Brauer, J. Buer, A. Scheffold, and A. Hamann: Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells The Journal of Experimental Medicine 199: 303, 2004.
Debes, G.F., K. Bonhagen, T. Wolff, U. Kretschmer, S. Krautwald, T. Kamradt and A. Hamann.: CC-chemokine receptor 7 expression by effector/memory CD4+ T cells depends on antigen-specificity and tissue localization during influenza A virus infection Journal of Virology 78: 7528, 2004.