PMID- 28130292
OWN - NLM
STAT- MEDLINE
DCOM- 20170526
LR  - 20220409
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 216
IP  - 3
DP  - 2017 Mar 6
TI  - Transcriptional determinants of tolerogenic and immunogenic states during 
      dendritic cell maturation.
PG  - 779-792
LID - 10.1083/jcb.201512012 [doi]
AB  - Dendritic cells (DCs) promote either tolerogenic or immunogenic T cell responses, 
      the latter upon sensing microbes. Using an in vitro system, we analyzed 
      transcriptional determinants that enable mature DCs to direct these opposing T 
      cell outcomes. In the absence of microbial products, the transcription factor 
      interferon regulatory factor 4 (IRF4) promotes regulatory T cell (T(reg)) 
      generation by enhancing expression of genes required for antigen presentation 
      along with those for T cell tolerance. IRF4-deficient DCs were impaired for 
      T(reg) generation in vivo. When exposed to microbial stimuli, DCs activated 
      nuclear factor (NF)-kappaB, which induced expression of a proinflammatory cytokine 
      module that, along with the antigen presentation module, promoted the generation 
      of effector T cells. NF-kappaB was, however, dispensable for T(reg) development. 
      Chromatin profiling revealed transcriptional motifs associated with the divergent 
      DC programs. Thus, DCs modulate their ability to prime tolerogenic or immunogenic 
      T cells by expressing a core antigen presentation module that is overlaid by 
      distinctive regulatory modules to promote either tolerance or immunity.
CI  - (c) 2017 Genentech.
FAU - Vander Lugt, Bryan
AU  - Vander Lugt B
AD  - Department of Cancer Immunology, Genentech, South San Francisco, CA 94080.
FAU - Riddell, Jeremy
AU  - Riddell J
AD  - Center for Autoimmune Genomics and Etiology, Divisions of Biomedical Informatics 
      and Developmental Biology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH 45229.
FAU - Khan, Aly A
AU  - Khan AA
AD  - Institute for Systems and Genomics Biology, The University of Chicago, Chicago, 
      IL 60637.
AD  - Department of Human Genetics, The University of Chicago, Chicago, IL 60637.
FAU - Hackney, Jason A
AU  - Hackney JA
AUID- ORCID: 0000-0002-5922-563X
AD  - Department of Bioinformatics and Computational Biology, Genentech, South San 
      Francisco, CA 94080.
FAU - Lesch, Justin
AU  - Lesch J
AD  - Department Translational Immunology, Genentech, South San Francisco, CA 94080.
FAU - DeVoss, Jason
AU  - DeVoss J
AD  - Department Translational Immunology, Genentech, South San Francisco, CA 94080.
FAU - Weirauch, Matthew T
AU  - Weirauch MT
AD  - Center for Autoimmune Genomics and Etiology, Divisions of Biomedical Informatics 
      and Developmental Biology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH 45229.
FAU - Singh, Harinder
AU  - Singh H
AD  - Center for Systems Immunology, Division of Immunobiology, Cincinnati Children's 
      Hospital Medical Center, Cincinnati, OH 45229 harinder.singh@cchmc.org 
      mellman.ira@gene.com.
FAU - Mellman, Ira
AU  - Mellman I
AD  - Department of Cancer Immunology, Genentech, South San Francisco, CA 94080 
      harinder.singh@cchmc.org mellman.ira@gene.com.
LA  - eng
PT  - Journal Article
DEP - 20170127
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Cytokines)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (NF-kappa B)
RN  - 0 (interferon regulatory factor-4)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/genetics/immunology
MH  - Cell Differentiation/genetics/immunology
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/metabolism/*physiology
MH  - Immune Tolerance/*genetics/*immunology/physiology
MH  - Interferon Regulatory Factors/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - T-Lymphocytes, Regulatory/immunology/metabolism/physiology
MH  - Transcription, Genetic/*genetics/immunology
PMC - PMC5350508
EDAT- 2017/01/29 06:00
MHDA- 2017/05/27 06:00
PMCR- 2017/03/06
CRDT- 2017/01/29 06:00
PHST- 2015/12/03 00:00 [received]
PHST- 2016/10/21 00:00 [revised]
PHST- 2016/12/30 00:00 [accepted]
PHST- 2017/01/29 06:00 [pubmed]
PHST- 2017/05/27 06:00 [medline]
PHST- 2017/01/29 06:00 [entrez]
PHST- 2017/03/06 00:00 [pmc-release]
AID - jcb.201512012 [pii]
AID - 201512012 [pii]
AID - 10.1083/jcb.201512012 [doi]
PST - ppublish
SO  - J Cell Biol. 2017 Mar 6;216(3):779-792. doi: 10.1083/jcb.201512012. Epub 2017 Jan 
      27.