PMID- 30885844
OWN - NLM
STAT- MEDLINE
DCOM- 20200521
LR  - 20200521
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 80
DP  - 2019 Aug
TI  - Apical splenic nerve electrical stimulation discloses an anti-inflammatory 
      pathway relying on adrenergic and nicotinic receptors in myeloid cells.
PG  - 238-246
LID - S0889-1591(18)31246-7 [pii]
LID - 10.1016/j.bbi.2019.03.015 [doi]
AB  - The autonomic nervous system innervates all lymphoid tissues including the spleen 
      therefore providing a link between the central nervous system and the immune 
      system. The only known mechanism of neural inhibition of inflammation in the 
      spleen relies on the production of norepinephrine by splenic catecholaminergic 
      fibers which binds to beta2-adrenergic receptors (beta 2-ARs) of CD4(+) T cells. These 
      CD4(+) T cells trigger the release of acetylcholine that inhibits the secretion 
      of inflammatory cytokines by macrophages through alpha7 nicotinic acetylcholine 
      receptor (alpha7nAchRs) signaling. While the vagal anti-inflammatory pathway has been 
      extensively studied in rodents, it remains to be determined whether it coexists 
      with other neural pathways. Here, we have found that three nerve branches project 
      to the spleen in mice. While two of these nerves are associated with an artery 
      and contain catecholaminergic fibers, the third is located at the apex of the 
      spleen and contain both catecholaminergic and cholinergic fibers. We found that 
      electrical stimulation of the apical nerve, but not the arterial nerves, 
      inhibited inflammation independently of lymphocytes. In striking contrast to the 
      anti-inflammatory pathway mechanism described so far, we also found that the 
      inhibition of inflammation by apical nerve electrical stimulation relied on 
      signaling by both beta 2-ARs and alpha7nAchRs in myeloid cells, with these two signaling 
      pathways acting in parallel. Most importantly, apical splenic nerve electrical 
      stimulation mitigated clinical symptoms in a mouse model of rheumatoid arthritis 
      further providing the proof-of-concept that such an approach could be beneficial 
      in patients with Immune-mediated inflammatory diseases.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Guyot, Melanie
AU  - Guyot M
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Simon, Thomas
AU  - Simon T
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Panzolini, Clara
AU  - Panzolini C
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Ceppo, Franck
AU  - Ceppo F
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Daoudlarian, Douglas
AU  - Daoudlarian D
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Murris, Emilie
AU  - Murris E
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Macia, Eric
AU  - Macia E
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Abelanet, Sophie
AU  - Abelanet S
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Sridhar, Arun
AU  - Sridhar A
AD  - Galvani Bioelectronics, Stevenage, United Kingdom.
FAU - Vervoordeldonk, Margriet J
AU  - Vervoordeldonk MJ
AD  - Galvani Bioelectronics, Stevenage, United Kingdom.
FAU - Glaichenhaus, Nicolas
AU  - Glaichenhaus N
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France.
FAU - Blancou, Philippe
AU  - Blancou P
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, France. Electronic address: blancou@ipmc.cnrs.fr.
LA  - eng
PT  - Journal Article
DEP - 20190315
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (Receptors, Adrenergic)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - N9YNS0M02X (Acetylcholine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Animals
MH  - Electric Stimulation
MH  - Female
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myeloid Cells/*immunology
MH  - Norepinephrine/metabolism
MH  - Receptors, Adrenergic/*immunology
MH  - Receptors, Nicotinic/*immunology
MH  - Spleen/*immunology/*innervation/physiopathology
MH  - Tumor Necrosis Factor-alpha/immunology
MH  - Vagus Nerve/immunology
MH  - Vagus Nerve Stimulation
OTO - NOTNLM
OT  - Anti-inflammatory pathway
OT  - Autonomous nervous system
OT  - Electrostimulation
OT  - Rheumatoid arthritis
OT  - Spleen
OT  - alpha7 acetylcholine receptor
OT  - beta2 adrenergic receptor
EDAT- 2019/03/20 06:00
MHDA- 2020/05/22 06:00
CRDT- 2019/03/20 06:00
PHST- 2018/12/21 00:00 [received]
PHST- 2019/03/07 00:00 [revised]
PHST- 2019/03/14 00:00 [accepted]
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2020/05/22 06:00 [medline]
PHST- 2019/03/20 06:00 [entrez]
AID - S0889-1591(18)31246-7 [pii]
AID - 10.1016/j.bbi.2019.03.015 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2019 Aug;80:238-246. doi: 10.1016/j.bbi.2019.03.015. Epub 2019 
      Mar 15.