My laboratory studies dendritic cell (DC) function in aging and disease states including alcoholism and graft-versus-host disease.
Results from an adult mouse model of alcoholism in my laboratory indicate that chronic ethanol (EtOH) exposure results in decreased numbers and function of DC in peripheral lymphoid tissue and skin. 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. We have also observed DC defects in a mouse model of fetal/neonatal EtOH exposure, many months after the mice are no longer exposed to EtOH and are characterizing these defects, as they are not identical to those seen in the adult EtOH model.
My laboratory also studies the role DC play in the increased susceptibility of advanced age allogeneic hematopoietic cell transplant patients to graft versus host disease (GVHD). Evidence from our murine studies indicate that increased inflammatory cytokine production by older DC may play a key role. We are also studying the mechanism that allows regulatory DC to limit GVHD toxicity while maintaining immunocompetence to infection, as a potential treatment for this disease, and studying human regulatory DC to determine whether they can be grown under clinically relevant conditions. 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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