PMID- 25582338
OWN - NLM
STAT- MEDLINE
DCOM- 20160217
LR  - 20181113
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 93
IP  - 5
DP  - 2015 May-Jun
TI  - STAT3 signaling contributes to the high effector activities of 
      interleukin-15-derived dendritic cells.
PG  - 461-71
LID - 10.1038/icb.2014.103 [doi]
AB  - Dendritic cells (DCs) are important innate and adaptive immune effectors, and 
      have a key role in antigen presentation and T-cell activation. Different lineages 
      of DCs can be developed from hematopoietic progenitors following cytokine 
      signaling, and the various lineages of DCs display distinct morphology, phenotype 
      and functions. There has been limited information on differential 
      cytokine-mediated molecular signaling in DCs. Analyses of surface molecules by 
      flow cytometry and quantitative RNA profiling revealed differences between DCs 
      derived from interleukin-4 (IL-4) versus IL-15 signaling, yet both lineages of 
      DCs exhibited similar levels of surface molecules key to immune activation. 
      Functional assays confirmed that IL-15-derived DCs elicited greater 
      antigen-specific, primary and secondary CD8 and CD4 T-cell responses than did 
      IL-4-derived DCs. Importantly, IL-15 DCs secreted substantial amounts of 
      proinflammatory cytokines, including IL-6, interferon-gamma (IFN-gamma) and tumor 
      necrosis factor-alpha (TNFalpha), which helped polarize a strong T-cell response. 
      Assessment of signaling pathways revealed that IL-15 DCs exhibited a lower levels 
      of activated signal transducer and activator of transcription 5 (STAT5), STAT6 
      and extracellular signal-regulated kinase 1/2 than IL-4 DCs, but after 
      lipopolysaccharide (LPS)/TNFalpha treatment, the STAT3 and p38 mitogen-activated 
      protein kinase (MAPK) activities were significantly enhanced in the IL-15 DCs. 
      Surprisingly, contrary to the canonical IL-15-mediated STAT5 signaling pathway in 
      lymphoid cells, IL-15 did not mediate a strong STAT5 or STAT3 activation in DCs. 
      Further analysis using specific inhibitors to STAT3 and p38 MAPK pathways 
      revealed that the STAT3 signaling, but not p38 MAPK signaling, contributed to 
      IFN-gamma production in DCs. Therefore, while IL-15 does not promote the STAT 
      signaling in DCs, the increased STAT3 activity after LPS/TNFalpha treatment of the 
      IL-15 DCs has a key role in their high IFN-gamma effector activities.
FAU - Okada, Starlyn
AU  - Okada S
AD  - Department of Molecular Genetics and Microbiology, College of Medicine, 
      University of Florida, Gainesville, FL, USA.
FAU - Han, Shuhong
AU  - Han S
AD  - Department of Molecular Genetics and Microbiology, College of Medicine, 
      University of Florida, Gainesville, FL, USA.
FAU - Patel, Ekta S
AU  - Patel ES
AD  - Department of Molecular Genetics and Microbiology, College of Medicine, 
      University of Florida, Gainesville, FL, USA.
FAU - Yang, Li-Jun
AU  - Yang LJ
AD  - Department of Pathology and Laboratory Medicine, College of Medicine, University 
      of Florida, Gainesville, FL, USA.
FAU - Chang, Lung-Ji
AU  - Chang LJ
AD  - Department of Molecular Genetics and Microbiology, College of Medicine, 
      University of Florida, Gainesville, FL, USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150113
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Interleukin-15)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT5 Transcription Factor)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-15/*metabolism
MH  - Lipopolysaccharides/immunology
MH  - Lymphocyte Activation
MH  - STAT3 Transcription Factor/*metabolism
MH  - STAT5 Transcription Factor/metabolism
MH  - Signal Transduction
PMC - PMC4450366
EDAT- 2015/01/15 06:00
MHDA- 2016/02/18 06:00
PMCR- 2015/06/01
CRDT- 2015/01/14 06:00
PHST- 2014/03/28 00:00 [received]
PHST- 2014/11/04 00:00 [revised]
PHST- 2014/11/13 00:00 [accepted]
PHST- 2015/01/14 06:00 [entrez]
PHST- 2015/01/15 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - icb2014103 [pii]
AID - 10.1038/icb.2014.103 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2015 May-Jun;93(5):461-71. doi: 10.1038/icb.2014.103. Epub 
      2015 Jan 13.