Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ.
Adrenergic Agents
/ metabolism
Animals
Antigens
/ immunology
Autoimmunity
Axotomy
CD8-Positive T-Lymphocytes
/ immunology
Denervation
Inflammation
/ pathology
Interferon-gamma
/ metabolism
Lymph Nodes
/ pathology
Male
Mice, Inbred C57BL
Peripheral Nerve Injuries
/ pathology
Sciatic Nerve
/ immunology
Signal Transduction
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
02 08 2021
02 08 2021
Historique:
received:
07
11
2020
revised:
19
02
2021
accepted:
03
05
2021
entrez:
4
6
2021
pubmed:
5
6
2021
medline:
3
11
2021
Statut:
ppublish
Résumé
Peripheral nerve injury can cause debilitating disease and immune cell-mediated destruction of the affected nerve. While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-γ in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-γ expression and expansion can be rescued by β2 adrenergic receptor agonists but not sensory nerve agonists. These data demonstrate the mechanisms governing the pro-inflammatory effect of loss of direct adrenergic input on lymph node function.
Identifiants
pubmed: 34086056
pii: 212257
doi: 10.1084/jem.20202377
pmc: PMC8185988
pii:
doi:
Substances chimiques
Adrenergic Agents
0
Antigens
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
ID : 635872
Pays : International
Informations de copyright
© 2021 Chen et al.
Déclaration de conflit d'intérêts
Disclosures: B. Schraml reported that the Schraml lab received funding from the Deutsche Forschungsgemeinschaft Projektnummer 360372040 - SFB 1335 (project 8; to B. Schraml). No other disclosures were reported.
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