Address for correspondence: Laura Beretta, Department of Microbiology and Immunology, University of Michigan, 6744 MSII, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-0620. Voice: 734 615 5964; fax: 734 615 6150.
berettal{at}umich.edu
Ann. N.Y. Acad. Sci. 975: 91-100 (2002).
Dendritic cells (DCs) are antigen-presenting cells that play
a major role in initiating primary immune responses. Their phenotypic
and functional characteristics are intimately linked to their
stage of maturation. The specific biochemical pathways and genes
whose expression mediates differentiation of progenitors to
DCs and their maturation are largely undefined. We recently
utilized two approaches, DNA microarrays and proteomics, to
analyze the expression profile of human CD14
+ blood monocytes
and their derived DCs. Approximately 4% of the genes or proteins
expressed were found to be regulated during DC differentiation.
Most of these genes were not previously associated with DCs
and included genes highly relevant to DC functions (genes involved
in antigen presentation, cell adhesion and motility, lipid metabolism).
Genes involved in specific signaling pathways, including I
B
,
PPAR-
and C/EBP
as well as two members of the family of transcription
factors, interferon regulatory factors (IRFs), were also modified.
Modulation of IRF gene expression is of particular interest
because of their functional roles in innate and adaptive immune
responses. IRF-family members control the expression of proteins
that include type-1 interferons, interleukin-12, interleukin-15,
MHC molecules and adhesion molecules. They have also been found
to play an important role in lymphocyte development. In contrast
to DC differentiation, very few genes were modified at the transcript
level during DC maturation as determined by microarray experiments.
Further analysis suggested that DC maturation is largely controlled
by posttranscriptional and posttranslational modifications.
The use of proteomics is therefore necessary for a full comprehension
of DC maturation process.
