Restoration of Regulatory T-Cell Function in Dry Eye Disease by Antagonizing Substance P/Neurokinin-1 Receptor.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
31
12
2019
revised:
28
04
2020
accepted:
05
05
2020
pubmed:
1
6
2020
medline:
22
9
2020
entrez:
1
6
2020
Statut:
ppublish
Résumé
Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. This study examined the phenotypic and functional changes in Tregs in response to SP in DED. The in vitro cultures of normal Tregs in the presence of SP led to a significant reduction in both Treg frequencies and their suppressive function, which was prevented by the addition of an SP receptor (neurokinin-1 receptor) antagonist. Furthermore, in vivo treatment with the neurokinin-1 receptor antagonist in DED mice effectively restored Treg function, suppressed pathogenic T helper 17 response, and significantly ameliorated the disease. Our results show that a significant increase in SP levels promotes Treg dysfunction in DED, and blockade of SP effectively restores Treg function and suppresses DED severity.
Identifiants
pubmed: 32473919
pii: S0002-9440(20)30254-6
doi: 10.1016/j.ajpath.2020.05.011
pmc: PMC7456741
pii:
doi:
Substances chimiques
Neurokinin-1 Receptor Antagonists
0
Receptors, Neurokinin-1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1859-1866Subventions
Organisme : NEI NIH HHS
ID : P30 EY003790
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY020889
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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