PMID- 23365459
OWN - NLM
STAT- MEDLINE
DCOM- 20130628
LR  - 20221109
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 121
IP  - 15
DP  - 2013 Apr 11
TI  - Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type 1 
      immunity by licensing host dendritic cells to produce IL-12.
PG  - 2923-33
LID - 10.1182/blood-2012-07-446054 [doi]
AB  - Substance-P and hemokinin-1 are proinflammatory neuropeptides with potential to 
      promote type 1 immunity through agonistic binding to neurokinin-1 receptor 
      (NK1R). Dendritic cells (DCs) are professional antigen-presenting cells that 
      initiate and regulate the outcome of innate and adaptive immune responses. 
      Immunostimulatory DCs are highly desired for the development of positive 
      immunization techniques. DCs express functional NK1R; however, regardless of 
      their potential DC-stimulatory function, the ability of NK1R agonists to promote 
      immunostimulatory DCs remains unexplored. Here, we demonstrate that NK1R 
      signaling activates therapeutic DCs capable of biasing type 1 immunity by 
      inhibition of interleukin-10 (IL-10) synthesis and secretion, without affecting 
      their low levels of IL-12 production. The potent type 1 effector immune response 
      observed following cutaneous administration of NK1R-signaled DCs required their 
      homing in skin-draining lymph nodes (sDLNs) where they induced inflammation and 
      licensed endogenous-conventional sDLN-resident and -recruited inflammatory DCs to 
      secrete IL-12. Our data demonstrate that NK1R signaling promotes 
      immunostimulatory DCs, and provide relevant insight into the mechanisms used by 
      neuromediators to regulate innate and adaptive immune responses.
FAU - Janelsins, Brian M
AU  - Janelsins BM
AD  - Department of Dermatology, University of Pittsburgh, 200 Lothrop St, Pittsburgh, 
      PA 15213, USA.
FAU - Sumpter, Tina L
AU  - Sumpter TL
FAU - Tkacheva, Olga A
AU  - Tkacheva OA
FAU - Rojas-Canales, Darling M
AU  - Rojas-Canales DM
FAU - Erdos, Geza
AU  - Erdos G
FAU - Mathers, Alicia R
AU  - Mathers AR
FAU - Shufesky, William J
AU  - Shufesky WJ
FAU - Storkus, Walter J
AU  - Storkus WJ
FAU - Falo, Louis D Jr
AU  - Falo LD Jr
FAU - Morelli, Adrian E
AU  - Morelli AE
FAU - Larregina, Adriana T
AU  - Larregina AT
LA  - eng
GR  - P50 CA121973/CA/NCI NIH HHS/United States
GR  - R01 AI077511/AI/NIAID NIH HHS/United States
GR  - AI077511/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130130
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Receptors, Neurokinin-1)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Blood. 2013 Apr 11;121(15):2815-6. PMID: 23580632
MH  - Animals
MH  - Bone Marrow Cells/immunology/metabolism
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/immunology/metabolism
MH  - Dendritic Cells/*immunology/metabolism/transplantation
MH  - Flow Cytometry
MH  - Immunity, Cellular/*immunology
MH  - Immunization/methods
MH  - Immunophenotyping
MH  - Interleukin-10/immunology/metabolism
MH  - Interleukin-12/genetics/*immunology/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Multiprotein Complexes/immunology/metabolism
MH  - Receptors, Neurokinin-1/agonists/*immunology/metabolism
MH  - Signal Transduction/immunology
MH  - TOR Serine-Threonine Kinases/immunology/metabolism
PMC - PMC3624938
EDAT- 2013/02/01 06:00
MHDA- 2013/07/03 06:00
PMCR- 2014/04/11
CRDT- 2013/02/01 06:00
PHST- 2013/02/01 06:00 [entrez]
PHST- 2013/02/01 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
PHST- 2014/04/11 00:00 [pmc-release]
AID - S0006-4971(20)49805-2 [pii]
AID - 2012/446054 [pii]
AID - 10.1182/blood-2012-07-446054 [doi]
PST - ppublish
SO  - Blood. 2013 Apr 11;121(15):2923-33. doi: 10.1182/blood-2012-07-446054. Epub 2013 
      Jan 30.