Sympathetic nervous system controls resolution of inflammation via regulation of repulsive guidance molecule A

The bidirectional communication between the immune and nervous system is important in regulating immune responses. Here we show that the adrenergic nerves of sympathetic nervous system orchestrate inflammation resolution and regenerative programs by modulating repulsive guidance molecule A (RGM-A). In murine peritonitis, adrenergic nerves and RGM-A show bidirectional activation by stimulating the mutual expression and exhibit a higher potency for the cessation of neutrophil infiltration; this reduction is accompanied by increased pro-resolving monocyte or macrophage recruitment, polymorphonucleocyte clearance and specialized pro-resolving lipid mediators production at sites of injury. Chemical sympathectomy results in hyperinflammation and ineffective resolution in mice, while RGM-A treatments reverse these phenotypes. Signalling network analyses imply that RGM-A and β2AR agonist regulate monocyte activation by suppressing NF-κB activity but activating RICTOR and PI3K/AKT signalling. Our results thus illustrate the function of sympathetic nervous system and RGM-A in regulating resolution and tissue repair in a murine acute peritonitis model.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Nature communications - 10(2019), 1 vom: 07. Feb., Seite 633

Sprache:

Englisch

Beteiligte Personen:

Körner, Andreas [VerfasserIn]
Schlegel, Martin [VerfasserIn]
Kaussen, Torsten [VerfasserIn]
Gudernatsch, Verena [VerfasserIn]
Hansmann, Georg [VerfasserIn]
Schumacher, Timo [VerfasserIn]
Giera, Martin [VerfasserIn]
Mirakaj, Valbona [VerfasserIn]

Links:

Volltext

Themen:

EC 2.7.1.-
EC 2.7.11.1
GPI-Linked Proteins
Journal Article
NF-kappa B
Nerve Tissue Proteins
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Research Support, Non-U.S. Gov't
Rgma protein, mouse

Anmerkungen:

Date Completed 08.04.2019

Date Revised 09.03.2020

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-019-08328-5

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM293594244