PMID- 15728463
OWN - NLM
STAT- MEDLINE
DCOM- 20050419
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 174
IP  - 5
DP  - 2005 Mar 1
TI  - IFN regulatory factor-4 and -8 govern dendritic cell subset development and their 
      functional diversity.
PG  - 2573-81
AB  - Dendritic cells (DCs) are bone marrow (BM)-derived APCs central to both innate 
      and adaptive immunity. DCs are a heterogeneous cell population composed of 
      multiple subsets with diverse functions. The mechanism governing the generation 
      of multiple DC subsets is, however, poorly understood. In this study we 
      investigated the roles of closely related transcription factors, IFN regulatory 
      factor (IRF)-4 and IRF-8, in DC development by analyzing IRF-4(-/-), IRF-8(-/-), 
      and IRF-4(-/-)IRF-8(-/-) (double-knockout) mice. We found that IRF-4 is required 
      for the generation of CD4(+) DCs, whereas IRF-8 is, as reported previously, 
      essential for CD8alpha(+) DCs. Both IRFs support the development of 
      CD4(-)CD8alpha(-) DCs. IRF-8 and, to a lesser degree, IRF-4 contribute to 
      plasmacytoid DC (PDC) development. Thus, the two IRFs together regulate the 
      development of all conventional DCs as well as PDCs. Consistent with these 
      findings, IRF-4, but not IRF-8, was expressed in CD4(+) DCs, whereas only IRF-8 
      was expressed in CD8alpha(+) DCs. CD4(-)CD8alpha(-) DCs and PDCs expressed both 
      IRFs. We also demonstrate in vitro that GM-CSF-mediated DC differentiation 
      depends on IRF-4, whereas Fms-like tyrosine kinase 3 ligand-mediated 
      differentiation depends mainly on IRF-8. Gene transfer experiments with 
      double-knockout BM cells showed that both IRFs have an overlapping activity and 
      stimulate a common process of DC development. Nonetheless, each IRF also 
      possesses a distinct activity to stimulate subset-specific gene expression, 
      leading to the generation of functionally divergent DCs. Together, IRF-4 and 
      IRF-8 serve as a backbone of the molecular program regulating DC subset 
      development and their functional diversity.
FAU - Tamura, Tomohiko
AU  - Tamura T
AD  - Laboratory of Molecular Growth Regulation, National Institute of Child Health and 
      Human Development, National Institutes of Health, Bethesda, MD 20892, USA. 
      tamurant@mail.nih.gov
FAU - Tailor, Prafullakumar
AU  - Tailor P
FAU - Yamaoka, Kunihiro
AU  - Yamaoka K
FAU - Kong, Hee Jeong
AU  - Kong HJ
FAU - Tsujimura, Hideki
AU  - Tsujimura H
FAU - O'Shea, John J
AU  - O'Shea JJ
FAU - Singh, Harinder
AU  - Singh H
FAU - Ozato, Keiko
AU  - Ozato K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Protein Subunits)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (interferon regulatory factor-4)
RN  - 0 (interferon regulatory factor-8)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics/*immunology
MH  - Cell Division/genetics/immunology
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/biosynthesis/deficiency/genetics/*physiology
MH  - Dendritic Cells/*cytology/*immunology/metabolism
MH  - Gene Expression Regulation/genetics/immunology
MH  - Interferon Regulatory Factors
MH  - Interferon-alpha/biosynthesis/deficiency
MH  - Interleukin-12/biosynthesis/deficiency
MH  - Interleukin-12 Subunit p40
MH  - Lymphocyte Activation/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Protein Subunits/biosynthesis/deficiency
MH  - Repressor Proteins/biosynthesis/genetics/*physiology
MH  - T-Lymphocytes, Helper-Inducer/cytology/immunology
MH  - Trans-Activators/biosynthesis/deficiency/genetics/*physiology
EDAT- 2005/02/25 09:00
MHDA- 2005/04/20 09:00
CRDT- 2005/02/25 09:00
PHST- 2005/02/25 09:00 [pubmed]
PHST- 2005/04/20 09:00 [medline]
PHST- 2005/02/25 09:00 [entrez]
AID - 174/5/2573 [pii]
AID - 10.4049/jimmunol.174.5.2573 [doi]
PST - ppublish
SO  - J Immunol. 2005 Mar 1;174(5):2573-81. doi: 10.4049/jimmunol.174.5.2573.