NK Cell IL-10 Production Requires IL-15 and IL-10 Driven STAT3 Activation

Sarah E. Clark, Kristina S. Burrack, Stephen C. Jameson, Sara E. Hamilton, Laurel L. Lenz

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Natural killer (NK) cells can produce IFNγ or IL-10 to regulate inflammation and immune responses but the factors driving NK cell IL-10 secretion are poorly-defined. Here, we identified NK cell-intrinsic STAT3 activation as vital for IL-10 production during both systemic Listeria monocytogenes (Lm) infection and following IL-15 cytokine/receptor complex (IL15C) treatment for experimental cerebral malaria (ECM). In both contexts, conditional Stat3 deficiency in NK cells abrogated production of IL-10. Initial NK cell STAT3 phosphorylation was driven by IL-15. During Lm infection, this required capture or presentation of IL-15 by NK cell IL-15Rα. Persistent STAT3 activation was required to drive measurable IL-10 secretion and required NK cell expression of IL-10Rα. Survival-promoting effects of IL-15C treatment in ECM were dependent on NK cell Stat3 while NK cell-intrinsic deficiency for Stat3, Il15ra, or Il10ra abrogated NK cell IL-10 production and increased resistance against Lm. NK cell Stat3 deficiency did not impact production of IFNγ, indicating the STAT3 activation initiated by IL-15 and amplified by IL-10 selectively drives the production of anti-inflammatory IL-10 by responding NK cells.

Original languageEnglish (US)
Article number2087
JournalFrontiers in immunology
Volume10
DOIs
StatePublished - Sep 4 2019

Keywords

  • IL-10
  • IL-15
  • IL-15 complex
  • Listeria (L.) monocytogenes
  • NK cell
  • Plasmodium
  • Stat3
  • cerebral malaria

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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