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 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, especially the skin. Currently, we are interested in defining the molecules involved in lymphocyte exit from extralymphoid tissues and the significance of this process to both protective and pathologic tissue immune responses. Another main interest of the lab is to determine the lymphocyte subsets involved in organ-specific immunity, with a focus on mobile surveillance mechanisms.
A major strength of my laboratory is the unique use of comparative immunology approaches in our research. Specifically, we complement in vivo mouse models with a classic model of lymph cannulation in the sheep that allows us to analyze cell compartments that are inaccessible in rodents or humans. In addition, we analyze human specimens to address whether our findings in ovine and mouse systems are relevant to human health. Finally, we are also committed to advancing general knowledge of the ruminant immune system, as domesticated ruminants are of worldwide importance.
Understanding the mechanisms involved in lymphocyte trafficking and recirculation through different organs not only reveals important components in the pathogenesis of inflammatory and infectious diseases, it also provides tools to therapeutically manipulate protective and pathogenic immune responses.
• Mechanisms of T lymphocyte exit from the inflamed skin during inflammation.
• Significance of T cell egress from skin to the course of inflammation.
• Trafficking of B1(-like) B cells into skin and other effector sites.
• Regulation of extramedullary accumulation of antibody secreting cells in the skin.
• Recirculation strategies of innate lymphocyte subsets.
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.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.Jennrich S., M.H. Lee, R.C. Lynn, K. Dewberry, and G.F. Debes Tissue exit – a novel control point in the accumulation of antigen-specific CD8 T cells in the influenza A virus-infected lung Journal of Virology 86: 3436, 2012.Geherin, S.A., S.R. Fintushel, M.H. Lee, R.P. Wilson, R.T. Patel, C. Alt, A.J. Young, J.B. Hay, and G.F. Debes The skin, a novel niche for recirculating B cells. The Journal of Immunology 188: 6027-6035, 2012.Geherin, S.A., M.H. Lee, R. Paul Wilson and G.F. Debes Ovine skin-recirculating ?d T cells express IFN-? and IL-17 and exit tissue independently of CCR7 Veterinary Immunology and Immunopathology 155: 87, 2013.