IL-24 intrinsically regulates Th17 cell pathogenicity in mice.
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:
01 08 2022
01 08 2022
Historique:
received:
08
12
2021
revised:
03
05
2022
accepted:
14
06
2022
entrez:
12
7
2022
pubmed:
13
7
2022
medline:
15
7
2022
Statut:
ppublish
Résumé
In certain instances, Th17 responses are associated with severe immunopathology. T cell-intrinsic mechanisms that restrict pathogenic effector functions have been described for type 1 and 2 responses but are less well studied for Th17 cells. Here, we report a cell-intrinsic feedback mechanism that controls the pathogenicity of Th17 cells. Th17 cells produce IL-24, which prompts them to secrete IL-10. The IL-10-inducing function of IL-24 is independent of the cell surface receptor of IL-24 on Th17 cells. Rather, IL-24 is recruited to the inner mitochondrial membrane, where it interacts with the NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 13 (also known as Grim19), a constituent of complex I of the respiratory chain. Together, Grim19 and IL-24 promote the accumulation of STAT3 in the mitochondrial compartment. We propose that IL-24-guided mitochondrial STAT3 constitutes a rheostat to blunt extensive STAT3 deflections in the nucleus, which might then contribute to a robust IL-10 response in Th17 cells and a restriction of immunopathology in experimental autoimmune encephalomyelitis.
Identifiants
pubmed: 35819408
pii: 213347
doi: 10.1084/jem.20212443
pmc: PMC9280194
pii:
doi:
Substances chimiques
Cytokines
0
Il24 protein, mouse
0
Interleukin-10
130068-27-8
NADH, NADPH Oxidoreductases
EC 1.6.-
Grim19 protein, mouse
EC 1.6.5.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB1054-B06 (ID 210592381)
Organisme : European Research Council
ID : CoG 647215
Pays : International
Organisme : Hertie Network of Clinical Neuroscience
Informations de copyright
© 2022 Sie et al.
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