PMID- 23966624
OWN - NLM
STAT- MEDLINE
DCOM- 20131113
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 191
IP  - 6
DP  - 2013 Sep 15
TI  - Transcriptional regulation of IL-15 expression during hematopoiesis.
PG  - 3017-24
LID - 10.4049/jimmunol.1301389 [doi]
AB  - Dendritic cells (DCs) are the most commonly studied source of the cytokine IL-15. 
      Using an IL-15 reporter transgenic mouse, we have recently shown previously 
      unappreciated differences in the levels of IL-15 expressed by subsets of 
      conventional DCs (CD8(+) and CD8(-)). In this study, we show that IL-15 promoter 
      activity was differentially regulated in subsets of hematopoietically derived 
      cells with IL-15 expression largely limited to myeloid lineages. In contrast, 
      mature cells of the lymphoid lineages expressed little to no IL-15 activity. 
      Surprisingly, we discovered that hematopoietic stem cells (lineage(-)Sca-1(+)c-Kit(+)) 
      expressed high levels of IL-15, suggesting that IL-15 expression was extinguished 
      during lymphoid development. In the case of T cells, this downregulation was 
      Notch-dependent and occurred in a stepwise pattern coincident with increasing 
      maturation and commitment to a T cell fate. Finally, we further demonstrate that 
      IL-15 expression was also controlled throughout DC development, with key 
      regulatory activity of IL-15 production occurring at the pre-DC branch point, 
      leading to the generation of both IL-15(+)CD8(+) and IL-15((-)/low)CD8(-) DC subsets. 
      Thus, IL-15 expression is coordinated with cellular fate in myeloid versus 
      lymphoid immune cells.
FAU - Colpitts, Sara L
AU  - Colpitts SL
AD  - Department of Immunology, University of Connecticut Health Center, Farmington, CT 
      06030, USA.
FAU - Stonier, Spencer W
AU  - Stonier SW
FAU - Stoklasek, Thomas A
AU  - Stoklasek TA
FAU - Root, Sierra H
AU  - Root SH
FAU - Aguila, Hector Leonardo
AU  - Aguila HL
FAU - Schluns, Kimberly S
AU  - Schluns KS
FAU - Lefrancois, Leo
AU  - Lefrancois L
LA  - eng
GR  - T32 CA009598/CA/NCI NIH HHS/United States
GR  - U01 AI 095544/AI/NIAID NIH HHS/United States
GR  - R01 AI76457/AI/NIAID NIH HHS/United States
GR  - AI 070910/AI/NIAID NIH HHS/United States
GR  - R01 AI076457/AI/NIAID NIH HHS/United States
GR  - 1RC1HL100569/HL/NHLBI NIH HHS/United States
GR  - R01 AI051583/AI/NIAID NIH HHS/United States
GR  - U01 AI095544/AI/NIAID NIH HHS/United States
GR  - RC1 HL100569/HL/NHLBI NIH HHS/United States
GR  - R01 AI070910/AI/NIAID NIH HHS/United States
GR  - CA009598/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130821
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Interleukin-15)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Cell Differentiation/immunology
MH  - Cell Lineage
MH  - Cell Separation
MH  - Flow Cytometry
MH  - Gene Expression Regulation/*immunology
MH  - Hematopoiesis/*immunology
MH  - Hematopoietic Stem Cells/cytology/*immunology
MH  - Interleukin-15/*biosynthesis/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myeloid Cells/immunology
MH  - Transcription, Genetic
PMC - PMC3896262
MID - NIHMS509558
EDAT- 2013/08/24 06:00
MHDA- 2013/11/14 06:00
PMCR- 2014/09/15
CRDT- 2013/08/23 06:00
PHST- 2013/08/23 06:00 [entrez]
PHST- 2013/08/24 06:00 [pubmed]
PHST- 2013/11/14 06:00 [medline]
PHST- 2014/09/15 00:00 [pmc-release]
AID - jimmunol.1301389 [pii]
AID - 10.4049/jimmunol.1301389 [doi]
PST - ppublish
SO  - J Immunol. 2013 Sep 15;191(6):3017-24. doi: 10.4049/jimmunol.1301389. Epub 2013 
      Aug 21.