PMID- 23999499
OWN - NLM
STAT- MEDLINE
DCOM- 20131119
LR  - 20211021
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 210
IP  - 10
DP  - 2013 Sep 23
TI  - Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal 
      dendritic cells.
PG  - 1961-76
LID - 10.1084/jem.20122508 [doi]
AB  - Dendritic cells (DCs) comprise distinct populations with specialized 
      immune-regulatory functions. However, the environmental factors that determine 
      the differentiation of these subsets remain poorly defined. Here, we report that 
      retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC 
      (precursor of DC)-derived splenic CD11b(+)CD8alpha(-)Esam(high) DCs and the 
      developmentally related CD11b(+)CD103(+) subset within the gut. Whereas mice 
      deprived of RA signaling significantly lost both of these populations, neither 
      pre-DC-derived CD11b(-)CD8alpha(+) and CD11b(-)CD103(+) nor monocyte-derived 
      CD11b(+)CD8alpha(-)Esam(low) or CD11b(+)CD103(-) DC populations were deficient. In 
      fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts 
      resulted in near complete conversion of these cells into the CD11b(+)CD8alpha(-) 
      subset, whereas transfer into vitamin A-deficient (VAD) hosts caused diversion to 
      the CD11b(-)CD8alpha(+) lineage. As vitamin A is an essential nutrient, we evaluated 
      retinoid levels in mice and humans after radiation-induced mucosal injury and 
      found this conditioning led to an acute VAD state. Consequently, radiation led to 
      a selective loss of both RA-dependent DC subsets and impaired class II-restricted 
      auto and antitumor immunity that could be rescued by supplemental RA. These 
      findings establish a critical role for RA in regulating the homeostasis of 
      pre-DC-derived DC subsets and have implications for the management of patients 
      with immune deficiencies resulting from malnutrition and irradiation.
FAU - Klebanoff, Christopher A
AU  - Klebanoff CA
AD  - Clinical Investigator Development Program and 2 Experimental Transplantation and 
      Immunology Branch, 3 Center for Cancer Research, National Cancer Institute, 
      National Institutes of Health (NIH), Bethesda, MD 20892.
FAU - Spencer, Sean P
AU  - Spencer SP
FAU - Torabi-Parizi, Parizad
AU  - Torabi-Parizi P
FAU - Grainger, John R
AU  - Grainger JR
FAU - Roychoudhuri, Rahul
AU  - Roychoudhuri R
FAU - Ji, Yun
AU  - Ji Y
FAU - Sukumar, Madhusudhanan
AU  - Sukumar M
FAU - Muranski, Pawel
AU  - Muranski P
FAU - Scott, Christopher D
AU  - Scott CD
FAU - Hall, Jason A
AU  - Hall JA
FAU - Ferreyra, Gabriela A
AU  - Ferreyra GA
FAU - Leonardi, Anthony J
AU  - Leonardi AJ
FAU - Borman, Zachary A
AU  - Borman ZA
FAU - Wang, Jinshan
AU  - Wang J
FAU - Palmer, Douglas C
AU  - Palmer DC
FAU - Wilhelm, Christoph
AU  - Wilhelm C
FAU - Cai, Rongman
AU  - Cai R
FAU - Sun, Junfeng
AU  - Sun J
FAU - Napoli, Joseph L
AU  - Napoli JL
FAU - Danner, Robert L
AU  - Danner RL
FAU - Gattinoni, Luca
AU  - Gattinoni L
FAU - Belkaid, Yasmine
AU  - Belkaid Y
FAU - Restifo, Nicholas P
AU  - Restifo NP
LA  - eng
GR  - R01 AA017927/AA/NIAAA NIH HHS/United States
GR  - F30 DK094708/DK/NIDDK NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - F30-DK094708-02/DK/NIDDK NIH HHS/United States
GR  - R01 DK090522/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130902
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 11103-57-4 (Vitamin A)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/immunology
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Dendritic Cells/cytology/*immunology/*metabolism/radiation effects
MH  - Female
MH  - Histocompatibility Antigens Class II/immunology
MH  - Homeostasis/*immunology
MH  - Humans
MH  - Immunophenotyping
MH  - Intestinal Mucosa/metabolism
MH  - Intestines/immunology/radiation effects
MH  - Mice
MH  - Neoplasms/immunology/metabolism
MH  - Organ Specificity/immunology
MH  - Phenotype
MH  - Receptors, Retinoic Acid/metabolism
MH  - Signal Transduction
MH  - Spleen/immunology/metabolism/radiation effects
MH  - Tretinoin/*metabolism
MH  - Vitamin A/metabolism
MH  - Whole-Body Irradiation/adverse effects
PMC - PMC3782040
EDAT- 2013/09/04 06:00
MHDA- 2013/11/20 06:00
PMCR- 2014/03/23
CRDT- 2013/09/04 06:00
PHST- 2013/09/04 06:00 [entrez]
PHST- 2013/09/04 06:00 [pubmed]
PHST- 2013/11/20 06:00 [medline]
PHST- 2014/03/23 00:00 [pmc-release]
AID - jem.20122508 [pii]
AID - 20122508 [pii]
AID - 10.1084/jem.20122508 [doi]
PST - ppublish
SO  - J Exp Med. 2013 Sep 23;210(10):1961-76. doi: 10.1084/jem.20122508. Epub 2013 Sep 
      2.