PMID- 23696838
OWN - NLM
STAT- MEDLINE
DCOM- 20131223
LR  - 20240319
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - Notch ligand delta-like 4-pretreated dendritic cells alleviate allergic airway 
      responses by enhancing IL-10 production.
PG  - e63613
LID - 10.1371/journal.pone.0063613 [doi]
LID - e63613
AB  - The Notch pathway plays a role in the processes of cell proliferation, 
      differentiation, and apoptosis, which affect the development and function of 
      various organs. Dendritic cells (DCs), as professional antigen-presenting cells 
      (APCs), induce T cell activation and promote T cell differentiation by antigen 
      stimulation. Research has shown that Notch ligand delta-like 4 (Dll4) in APCs is 
      associated with stimulation of a Th1-type response. However, the regulatory roles 
      of Dll4 in the activation and function of DCs have yet to be clearly elucidated. 
      In this study, we demonstrated that activation of Dll4-pretreated bone 
      marrow-derived DCs by performing ovalbumin (OVA) stimulation expressed a high 
      level of interleukin (IL)-10 without diminishing IL-12 production. By contrast, 
      the proinflammatory cytokines, IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, 
      decreased in Dll4-pretreated DCs by performing either lipopolysaccharide (LPS) or 
      OVA stimulation. Compared to fully mature DCs, lower levels of MHC class II CD40 
      and higher levels of CD80 and CD86 molecules were expressed in these semi-mature 
      like DCs. Dll4 Notch signaling also enhanced Notch ligand mRNA expression of 
      Dll1, Dll4, and Jagged1 in DCs. Dll4-modified DCs exhibited a reduced capacity to 
      stimulate the proliferation of OVA-specific CD4(+) T cells, but actively promoted 
      large amounts of IL-10 production in these activated T cells. Furthermore, 
      immunomodulatory effects of Dll4-modified DCs were examined in an established 
      asthmatic animal model. After adoptive transfer of OVA-pulsed plus 
      Dll4-pretreated DCs in OVA-immunized mice, OVA challenge induced lower 
      OVA-specific immunoglobulin E (IgE) and higher IgG2a antibody production, lower 
      eotaxin, keratinocyte-derived chemokine (KC), IL-5, and IL-13 release in 
      bronchial alveolar lavage fluid, attenuated airway hyper-responsiveness, and 
      promoted higher IL-10 and interferon (IFN)-gamma production in the spleen. In 
      summary, our findings elucidate the new role of Dll4 in the phenotype and 
      function of DCs and provide a novel approach for manipulating T cell-driven 
      deleterious immune diseases.
FAU - Huang, Huei-Mei
AU  - Huang HM
AD  - Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
FAU - Hsiao, George
AU  - Hsiao G
FAU - Fan, Chia-Kwung
AU  - Fan CK
FAU - Lin, Chu-Lun
AU  - Lin CL
FAU - Leu, Sy-Jye
AU  - Leu SJ
FAU - Chiang, Bor-Luen
AU  - Chiang BL
FAU - Lee, Yueh-Lun
AU  - Lee YL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130516
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (delta protein)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
EIN - PLoS One. 2017 Oct 11;12 (10 ):e0186529. PMID: 29020050
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dendritic Cells/*drug effects/*immunology
MH  - Female
MH  - Interleukin-10/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/*pharmacology
MH  - Membrane Proteins/*pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
PMC - PMC3656003
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/23 06:00
MHDA- 2013/12/24 06:00
PMCR- 2013/05/16
CRDT- 2013/05/23 06:00
PHST- 2013/01/15 00:00 [received]
PHST- 2013/04/04 00:00 [accepted]
PHST- 2013/05/23 06:00 [entrez]
PHST- 2013/05/23 06:00 [pubmed]
PHST- 2013/12/24 06:00 [medline]
PHST- 2013/05/16 00:00 [pmc-release]
AID - PONE-D-13-02683 [pii]
AID - 10.1371/journal.pone.0063613 [doi]
PST - epublish
SO  - PLoS One. 2013 May 16;8(5):e63613. doi: 10.1371/journal.pone.0063613. Print 2013.