Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression.
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:
07 11 2022
07 11 2022
Historique:
received:
28
03
2022
revised:
14
06
2022
accepted:
05
08
2022
entrez:
6
9
2022
pubmed:
7
9
2022
medline:
9
9
2022
Statut:
ppublish
Résumé
Human adaptive-like natural killer (NK) cells express low levels of FcεRIγ (FcRγ-/low) and are reported to accumulate during COVID-19 infection; however, the mechanism underlying and regulating FcRγ expression in NK cells has yet to be fully defined. We observed lower FcRγ protein expression in NK cell subsets from lung transplant patients during rapamycin treatment, suggesting a link with reduced mTOR activity. Further, FcRγ-/low NK cell subsets from healthy donors displayed reduced mTOR activity. We discovered that FcRγ upregulation is dependent on cell proliferation progression mediated by IL-2, IL-15, or IL-12, is sensitive to mTOR suppression, and is inhibited by TGFβ or IFNα. Accordingly, the accumulation of adaptive-like FcRγ-/low NK cells in COVID-19 patients corresponded to increased TGFβ and IFNα levels and disease severity. Our results show that an adaptive-like NK cell phenotype is induced by diminished cell proliferation and has an early prognostic value for increased TGFβ and IFNα levels in COVID-19 infection associated with disease severity.
Identifiants
pubmed: 36066491
pii: 213443
doi: 10.1084/jem.20220551
pmc: PMC9448639
pii:
doi:
Substances chimiques
Transforming Growth Factor beta
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI068129
Pays : United States
Organisme : International Society for Heart and Lung Transplantation
Organisme : Cystic Fibrosis Foundation
ID : CALABR19Q0
Organisme : Irvington Cancer Research Institute
Organisme : CSRD VA
ID : I01 CX002011
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151552
Pays : United States
Organisme : BLRD VA
ID : IK2 BX005301
Pays : United States
Organisme : Parker Institute for Cancer Immunotherapy
Organisme : Office of Research and Development
ID : CX002011
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 Shemesh et al.
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