| First Author | Clark SE | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 2087 | PubMed ID | 31552035 |
| Mgi Jnum | J:296996 | Mgi Id | MGI:6471988 |
| Doi | 10.3389/fimmu.2019.02087 | Citation | Clark SE, et al. (2019) NK Cell IL-10 Production Requires IL-15 and IL-10 Driven STAT3 Activation. Front Immunol 10:2087 |
| abstractText | Natural killer (NK) cells can produce IFNgamma 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-15Ralpha. Persistent STAT3 activation was required to drive measurable IL-10 secretion and required NK cell expression of IL-10Ralpha. 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 IFNgamma, 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. |
