Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression

Avishai Shemesh, Yapeng Su, Daniel R. Calabrese, Daniel Chen, Janice Arakawa-Hoyt, Kole T. Roybal, James R. Heath, John R. Greenland, Lewis L. Lanier

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere20220551
JournalJournal of Experimental Medicine
Volume219
Issue number11
DOIs
StatePublished - 7 Nov 2022
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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