Annette Schlueter, MD, PhD
Research Laboratory
Contact Information
Phone: 319-335-7694
1117 Medical Laboratories
Dendritic Cell Function in Disease
My laboratory is interested in the contributions of dendritic cells (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, and the influence of aging on ex vivo-derived recipient regulatory DC ability to ameliorate graft vs. host disease (GVHD) following allogeneic hematopoietic cell transplant (HCT).
It is clear that chronic alcohol abuse results in immunodeficiency, characterized by loss of some lymphocyte subsets and persistent alterations in the function of other subsets. Evidence from our mouse model of alcoholism indicates that chronic ethanol feeding results in decreased numbers of DC in spleen and epidermis. These losses are partially due to defective DC migration in the presence of EtOH. EtOH-exposed DC are also unable to activate T cells appropriately, as a result of dysregulated costimulatory molecule expression and cytokine secretion. In addition, they increase the frequency of adaptive regulatory T cell formation. Preliminary evidence suggests that the mechanism for these changes may be EtOH induced increases in oxidative stress. We are investigating additional ways in which EtOH exposure in vivo may influence DC function, thereby increasing the susceptibility of alcoholics to infection. Additional studies are investigating the stability of these changes after EtOH cessation (modeling the recovered human alcoholic), and the effect of fetal and neonatal EtOH exposure on dendritic cell function (modeling human fetal alcohol exposure).
In separate studies, my laboratory is 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, but very little is known about the mechanism by which this occurs. 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, and have found that older DC subjected to HCT preparatory regimens are more likely to secrete immunostimulatory cytokines than young DC. Understanding functional changes in DC populations with age will allow us ultimately to design therapeutic interventions that may limit the toxicity of GVHD, and allow the life-saving therapy of HCT to be offered to more advanced age patients. Finally, we are investigating treatment of GVHD with cultured regulatory DC, to understand the mechanism by which this therapy ameliorates the disease and to determine if it is feasible to translate this therapy to humans.
(See complete publications list at PubMed)
Research Staff
Ruth A. Coleman, BS, MT(ASCP)
ruth-coleman@uiowa.edu
Research Specialist
319-335-7694
Corey Parlet, MS
corey-parlet@uiowa.edu
Graduate Research Assistant
319-335-6721
Sabrina Scroggins, BS
sabrina-scroggins@uiowa.edu
Graduate Research Assistant
319-335-6271