科研之友
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摘要
Background: Viral myocarditis is a widespread cardiac disease associated with inflammation and myocardial injury and is predominantly caused by coxsackievirus B3 (CVB3) infection in humans as well as in mice. CVB3-induced myocarditis shows sexually dimorphic sensitivity and is more prevalent in male mice. Our previous studies showed that natural killer (NK) cells played an indispensable role in CVB3-induced myocarditis, and female mice exhibited less pathological cardiac interferon gamma (IFN-gamma)(+) NK cell infiltration than did male mice. However, the precise mechanisms were not well elucidated. @@@ Methods: We investigated the influence of estrogen on cardiac IFN-gamma(+) NK cell enrichment in CVB3-induced myocarditis and explored the underlying molecular mechanism. @@@ Results: In this study, we found that CVB3 stimulation could clearly induce IFN-g expression by NK cells; however, this trend could be blunted by estrogen treatment. Consistently, ovariectomized female mice with decreased estrogen levels exhibited substantially increased enrichment of cardiac IFN-gamma(+) NK cells and displayed significantly aggravated myocarditis. Similarly, estrogen-treated male mice showed less cardiac IFN-gamma(+) NK cell infiltration, accompanied by significantly alleviated viral myocarditis. In sharp contrast, sexually immature female and male mice (with similar estrogen levels) showed comparable levels of cardiac IFN-gamma(+) NK cell infiltration and similar levels of myocarditis severity. Upon further exploration of the underlying mechanisms, we found that estrogen could downregulate expression of Th1-specific T box transcription factor (T-bet), the key transcription factor associated with IFN-gamma production, in CVB3-stimulated NK cells. @@@ Conclusions: Overall, this study might help us understand the mechanism of increased cardiac infiltration by IFN-gamma(+) NK cells in CVB3-infected male mice compared with that in female mice and might provide new clues for the sex bias in CVB3-induced myocarditis.
