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BIOGRAPHY:
Dr. Nagy received his Ph.D. in molecular biology in 1995 from the University Medical School of Debrecen in Hungary. He did postdoctoral work in the United States at the Salk Institute for Biological Studies and at the University of Texas Health Science Center in Houston, where he holds the title of Adjunct Professor. He has received a Szechenyi Fellowship and a Boehringer Ingelheim Research Award. He is currently Associate Professor in the Department of Biochemistry and Molecular Biology at the University of Debrecen, Medical and Health Sciences Center, in Hungary, where he is working on a project entitled " Nuclear Receptors Regulate Lineage Specification and the Function of
Antigen-Presenting Cells."
RESEARCH ABSTRACT SUMMARY:
Nuclear Receptors Regulate Lineage Specification and the Function of Antigen-Presenting Cells
Very little is known about the transcriptional events controlling
the differentiation and lineage commitment of monocyte-derived
dendritic cells (DCs) and their responses to external stimuli and/or
internal signals. In a search for such a mechanism, we found that the
ligand-activated transcription factor peroxisome proliferator activated
receptor gamma (PPARgamma) is immediately up-regulated after the
induction of the differentiation of monocyte-derived DCs by IL-4 and
GM-CSF. Activation of the PPARgamma receptor altered the phenotype of
DCs by changing the expression pattern of cell surface receptors
involved in various functions and enhanced the internalizing activity
and lysosomal marker expression of immature DCs. Unexpectedly, we found
that a class of molecules responsible for the presentation of self- and
foreign modified lipids were coordinately regulated by PPARgamma
activation. CD1a antigen levels were reduced, whereas CD1d expression
was induced. Enhanced expression of CD1d was coupled to the selective
induction of NKT cell proliferation in the presence of DCs exposed to
ligands of PPARgamma. Taken together, the results suggest that the
lipid-activated transcription factor PPARgamma is involved in
orchestrating a transcriptional response in differentiating DCs,
leading to lineage specification and to the development of a DC subtype
with increased internalizing capacity and specific lipid presentation
for NKT cells.
Photo: Kent Kallberg, Kallberg Studios
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