Targeting IFN-λ Signaling Promotes Recovery from Central Nervous System Autoimmunity.
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
15 03 2022
15 03 2022
Historique:
received:
29
10
2021
accepted:
07
01
2022
pubmed:
20
2
2022
medline:
20
4
2022
entrez:
19
2
2022
Statut:
ppublish
Résumé
Type III IFNs (IFNLs) are newly discovered cytokines, acting at epithelial and other barriers, that exert immunomodulatory functions in addition to their primary roles in antiviral defense. In this study, we define a role for IFNLs in maintaining autoreactive T cell effector function and limiting recovery in a murine model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis. Genetic or Ab-based neutralization of the IFNL receptor (IFNLR) resulted in lack of disease maintenance during experimental autoimmune encephalomyelitis, with loss of CNS Th1 effector responses and limited axonal injury. Phenotypic effects of IFNLR signaling were traced to increased APC function, with associated increase in T cell production of IFN-γ and GM-CSF. Consistent with this, IFNL levels within lesions of CNS tissues derived from patients with MS were elevated compared with MS normal-appearing white matter. Furthermore, expression of IFNLR was selectively elevated in MS active lesions compared with inactive lesions or normal-appearing white matter. These findings suggest IFNL signaling as a potential therapeutic target to prevent chronic autoimmune neuroinflammation.
Identifiants
pubmed: 35181638
pii: jimmunol.2101041
doi: 10.4049/jimmunol.2101041
pmc: PMC9012116
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1341-1351Subventions
Organisme : NINDS NIH HHS
ID : F31 NS108629
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS106289
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007200
Pays : United States
Organisme : NIAID NIH HHS
ID : K22 AI125466
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS059560
Pays : United States
Informations de copyright
Copyright © 2022 by The American Association of Immunologists, Inc.
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