Monocytic myeloid-derived suppressor cells from females, but not males, alleviate CVB3-induced myocarditis by increasing regulatory and CD4(+)IL-10(+) T cells.
Monocytic myeloid-derived suppressor cells from females, but not males, alleviate CVB3-induced myocarditis by increasing regulatory and CD4(+)IL-10(+) T cells.
复制标题
来自女性而非男性的单核细胞骨髓源性抑制细胞通过增加调节性 T 细胞和 CD4( )IL-10( ) T 细胞减轻 CVB3 诱导的心肌炎
DOI：
10.1038/srep22658
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发表时间：
2016-03-04
影响因子：
4.6
通讯作者：
Xiong S
中科院分区：
文献类型：
--
作者：
Su N;Yue Y;Xiong S
柯萨奇病毒B组3型（CVB 3）是病毒性心肌炎的常见病原体，常引起性二型心肌炎，男性发病率和死亡率较高。到目前为止，男性高患病率的潜在机制还没有得到很好的阐明。本研究通过比较骨髓源性抑制细胞（MDSCs）的频率、亚群以及免疫抑制功能，探讨MDSCs在CVB 3诱导的小鼠心肌炎性别偏倚中的作用。我们发现，在感染的女性中，心肌MDSC比男性富集得多，具有显著更高的CD 11b + Ly 6 G + Ly 6C高单核细胞亚群（M-MDSC）与CD 11b + Ly 6 G + Ly 6C低粒细胞亚群（G-MDSC）的百分比比率。有趣的是，在雌性来源的M-MDSC中也证明了对T细胞增殖的更有效抑制。一致的是，过继转移雌性而非雄性来源的M-MDSC有效地减轻了雄性受体小鼠中CVB 3诱导的心肌炎，并且这种保护可以归因于调节性T细胞和CD 4 +IL-10+ T细胞的诱导增加。我们的研究表明，心肌MDSCs不仅在数量上，而且在CVB 3感染的男性和女性的表型和免疫抑制功能的独特诱导;和女性衍生的更具抑制性的M-MDSCs有助于他们的不敏感性CVB 3诱导的心肌炎。
Coxsackievirus group B type 3 (CVB3) is a common etiologic agent of viral myocarditis and often causes sexually dimorphic myocarditis with increased incidence and mortality in male. So far, the underlying mechanism for the high male prevalence is not well elucidated. In this study, we deciphered the role of myeloid-derived suppressor cells (MDSCs) in the gender bias in murine CVB3-induced myocarditis by comparing their frequencies, subsets as well as immune suppressive functions. We found that much more myocardial MDSCs were enriched in infected females than males, with dramatically higher percentage ratio of CD11b+Ly6G-Ly6Chigh monocytic subset (M-MDSCs) to CD11b+Ly6G+Ly6Clow granulocytic subset (G-MDSCs). Interestingly, more potent suppression on T cell proliferation was also evidenced in female-derived M-MDSCs. Consistently, adoptive transfer of female- but not male-derived M-MDSCs efficiently alleviated CVB3-induced myocarditis in male recipient mice, and this protection could be ascribed to the increased induction of regulatory and CD4+IL-10+ T cells. Our study suggested that myocardial MDSCs were distinctively induced not only in quantities but also in phenotypes and immune suppressive functions in CVB3-infected males and females; and female-derived more suppressive M-MDSCs contributed to their insensitivity to CVB3-induced myocarditis.