PMID- 18987361
OWN - NLM
STAT- MEDLINE
DCOM- 20090501
LR  - 20221109
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 113
IP  - 13
DP  - 2009 Mar 26
TI  - Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote 
      survival of dendritic cells and potent cellular immunity.
PG  - 3017-26
LID - 10.1182/blood-2008-06-163121 [doi]
AB  - Dendritic cells (DCs) are the preferred targets for immunotherapy protocols 
      focused on stimulation of cellular immune responses. However, regardless of 
      initial promising results, ex vivo generated DCs do not always promote 
      immune-stimulatory responses. The outcome of DC-dependent immunity is regulated 
      by proinflammatory cytokines and neuropeptides. Proinflammatory neuropeptides of 
      the tachykinin family, including substance P (SP) and hemokinin-1 (HK-1), bind 
      the neurokinin 1 receptor (NK1R) and promote stimulatory immune responses. 
      Nevertheless, the ability of pro-inflammatory tachykinins to affect the immune 
      functions of DCs remains elusive. In the present work, we demonstrate that mouse 
      bone marrow-derived DCs (BMDCs) generated in the presence of granulocyte 
      macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), express 
      functional NK1R. Signaling via NK1R with SP, HK-1, or the synthetic agonist 
      [Sar(9)Met(O(2))(11)]-SP rescues DCs from apoptosis induced by deprivation of 
      GM-CSF and IL-4. Mechanistic analysis demonstrates that NK1R agonistic binding 
      promotes DC survival via PI3K-Akt signaling cascade. In adoptive transfer 
      experiments, NK1R-signaled BMDCs loaded with Ag exhibit increased longevity in 
      draining lymph nodes, resulting in enhanced and prolonged effector cellular 
      immunity. Our results contribute to the understanding of the interactions between 
      the immune and nervous systems that control DC function and present a novel 
      approach for ex vivo-generation of potent immune-stimulatory DCs.
FAU - Janelsins, Brian M
AU  - Janelsins BM
AD  - Department of Dermatology, University of Pittsburgh School of Medicine, PA, USA.
FAU - Mathers, Alicia R
AU  - Mathers AR
FAU - Tkacheva, Olga A
AU  - Tkacheva OA
FAU - Erdos, Geza
AU  - Erdos G
FAU - Shufesky, William J
AU  - Shufesky WJ
FAU - Morelli, Adrian E
AU  - Morelli AE
FAU - Larregina, Adriana T
AU  - Larregina AT
LA  - eng
GR  - T32 CA082084/CA/NCI NIH HHS/United States
GR  - R01 HL075512/HL/NHLBI NIH HHS/United States
GR  - R01 CA100893/CA/NCI NIH HHS/United States
GR  - R01-HL077545/HL/NHLBI NIH HHS/United States
GR  - R01-HL075512/HL/NHLBI NIH HHS/United States
GR  - R01-CA100893/CA/NCI NIH HHS/United States
GR  - T32-CA82084/CA/NCI NIH HHS/United States
GR  - R01 HL077545/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081105
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CD40 Antigens)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, Neurokinin-1)
RN  - 0 (Tachykinins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Apoptosis/drug effects/immunology
MH  - Bone Marrow Cells/metabolism
MH  - CD40 Antigens/metabolism/physiology
MH  - Cell Survival/drug effects/genetics
MH  - Dendritic Cells/*drug effects/metabolism/physiology/transplantation
MH  - Enzyme Activation/drug effects
MH  - Immunity, Cellular/*drug effects/genetics/physiology
MH  - Inflammation Mediators/metabolism/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Receptors, Neurokinin-1/agonists/genetics/metabolism/*physiology
MH  - Signal Transduction/drug effects/genetics/immunology
MH  - Tachykinins/metabolism/*pharmacology
PMC - PMC2662645
EDAT- 2008/11/07 09:00
MHDA- 2009/05/02 09:00
PMCR- 2010/03/26
CRDT- 2008/11/07 09:00
PHST- 2008/11/07 09:00 [pubmed]
PHST- 2009/05/02 09:00 [medline]
PHST- 2008/11/07 09:00 [entrez]
PHST- 2010/03/26 00:00 [pmc-release]
AID - S0006-4971(20)39421-0 [pii]
AID - 2008/163121 [pii]
AID - 10.1182/blood-2008-06-163121 [doi]
PST - ppublish
SO  - Blood. 2009 Mar 26;113(13):3017-26. doi: 10.1182/blood-2008-06-163121. Epub 2008 
      Nov 5.