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| My laboratory studies dendritic cell function in aging, and disease states including alcoholism and graft-versus-host disease. | ||||||
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My laboratory is interested in the contribution of dendritic cell (DC) to disease. Specifically, we study the defects induced in DC by chronic ethanol (EtOH) exposure that contribute to increased incidence and severity of infectious disease, the influence of aging on DC ability to induce more severe graft vs. host disease (GVHD) following allogeneic hematopoietic cell transplant (HCT), and the mechanisms by which regulatory DC (DCreg) can prevent severe GVHD.
It is clear that chronic alcohol abuse and fetal alcohol exposure result in immunodeficiency, characterized by loss of some lymphocyte subsets and persistent activation of other subsets. Results from an adult mouse model of alcoholism in my laboratory indicate that chronic ethanol exposure results in decreased numbers of DC in peripheral lymphoid tissue and epidermis. EtOH-exposed DC are also unable to appropriately activate naive T cells due to failure to upregulate costimulatory molecules and migrate at appropriate rates. In addition, these DC induce increased numbers of regulatory T cells. We are also investigating the mechanism by which in vivo EtOH exposure alters DC function, and have preliminary evidence that increased oxidative stress plays a role. My laboratory is also interested in understanding the role DC play in the increased susceptibility of advanced age allogeneic HCT patients to GVHD. It is clear that recipient DC play a key role in the development of GVHD, and evidence from our murine studies indicate that increased inflammatory cytokine production by older DC may play a role. We are studying the functional characteristics of DC from older and young HCT patients, as well as older and young mice in murine models of HCT. We are also studying the mechanism that allows Dcreg to limit GVHD toxicity, as a potential treatment for this disease. Understanding functional changes in these populations with age will allow us ultimately to design therapeutic interventions that may limit the toxicity of GVHD, and allow this life-saving therapy to be offered to more advanced age patients. |
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| Selected Publications | ||||||
| Click Here for a Complete List of Articles | ||||||
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McGill, J., Meyerholz, D., Edsen-Moore, M., Young, B., Coleman, R.A., Schlueter A., Waldschmidt, T.J., Cook, R.T. and Legge, K.L. Fetal exposure to ethanol has long-term effects on the severity of influenza virus infections. Journal of Immunology, 182:7803-7808, 2009.
Edsen-Moore, M.E., Fan, J., Ness, K.J., Marietta, J.R., Cook, R.T. and Schlueter A.J. The effects of chronic ethanol feeding on dendritic cell numbers, turnover rate, and dendropoiesis. Alcoholism: Clinical and Experimental Research 32:1309-1320, 2008. Ness, K.J., Fan, J., Wilke, W.W., Coleman, R.A., Cook, R.T. and Schlueter A.J. Chronic ethanol consumption decreases murine Langerhans cell numbers and delays migration of Langerhans cells as well as dermal dendritic cells. Alcoholism: Clinical and Experimental Research 32:657-668, 2008. Cook, R.T., Schlueter A.J., Coleman, R.A., Tygrett, L.T., Ballas, Z.K., Jerrells, T.R., Nashelsky, M.B., Ray, N.B., Haugen, T.H. and Waldschmidt, T.J. Thymocytes, pre-B cells and organ changes in a mouse model of chronic ethanol ingestion. Absence of subset-specific glucocorticoid-induced immune cell loss. Alcoholism: Clinical and Experimental Research, 31:1746-1758, 2007. Schlueter A.J. and Glasgow, J. Phenotypic comparison of multiple monocyte-related populations in murine peripheral blood and bone marrow. Cytometry 69A:281-290, 2006. |
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| Department/Program Affiliations |
| Pathology |
| Biosciences |
| Immunology |
| MSTP |