Gonadectomy of male BALB/c mice increases Tim-3(+) alternatively activated M2 macrophages, Tim-3(+) T cells, Th2 cells and Treg in the heart during acute coxsackievirus-induced myocarditis.
Gonadectomy of male BALB/c mice increases Tim-3(+) alternatively activated M2 macrophages, Tim-3(+) T cells, Th2 cells and Treg in the heart during acute coxsackievirus-induced myocarditis.
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DOI：
10.1016/j.bbi.2008.12.002
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发表时间：
2009-07
影响因子：
15.1
通讯作者：
Fairweather, DeLisa
中科院分区：
文献类型：
--
作者：
Frisancho-Kiss, Sylvia;Coronado, Michael J.;Frisancho, J. Augusto;Lau, Vivian M.;Rose, Noel R.;Klein, Sabra L.;Fairweather, DeLisa
心血管疾病，包括心肌炎等炎症性心脏病的发病率在男性中有所增加。同样，与雌性相比，感染柯萨奇病毒B3（CVB 3）的雄性BALB/c小鼠在心脏中发生更严重的急性炎症。为了更好地了解男性性激素对心脏炎症的影响，我们对雄性BALB/c小鼠进行了性腺切除（Gdx），并与假手术对照组相比，检查了急性CVB 3诱导的心肌炎。心脏中的病毒复制在Gdx和假手术小鼠之间没有显著改变。然而，性腺切除术显著降低了睾酮水平和心脏炎症。从心脏中分离的细胞群的FACS分析显示，Gdx雄性中的CD 11b+细胞显著减少。然而，CD 11b+细胞的GR 1 +F4/80+亚群显著增加。由于该亚群也表达白细胞介素（IL）-4R和IL-10，我们将这些细胞称为“交替激活”或M2巨噬细胞。Gdx雄性中表达抑制性受体Tim-3的M2巨噬细胞百分比较高，而表达IL-1β和IL-10的M2巨噬细胞百分比较少。只有M2巨噬细胞上调TLR 4和Tim-3，而GR 1 −IL-4 Rlo巨噬细胞没有。此外，Gdx后心脏中IL-4+ CD 4 + Th 2细胞、Foxp 3+调节性T（Treg）细胞和Tim-3+ CD 4 + T细胞显著增加。因此，我们首次报道抑制性受体Tim-3在M2巨噬细胞上表达。我们的研究结果表明，睾丸释放的性激素和/或其他介质抑制心脏中的抗炎细胞群，包括Tim-3+ M2、Tim-3+ CD 4 + T细胞、Th 2和Treg，导致男性在CVB 3感染后出现更严重的急性心脏炎症。
The incidence of cardiovascular disease, including inflammatory heart diseases like myocarditis, is increased in men. Similarly, male BALB/c mice infected with coxsackievirus B3 (CVB3) develop more severe acute inflammation in the heart compared to females. To better understand the effect of male sex hormones on cardiac inflammation, we gonadectomized (Gdx) male BALB/c mice and examined acute CVB3-induced myocarditis compared to sham controls. Viral replication in the heart was not significantly altered between Gdx and sham mice. However, gonadectomy significantly reduced testosterone levels and inflammation in the heart. FACS analysis of cell populations isolated from the heart revealed that CD11b+ cells were significantly reduced in Gdx males. However, a GR1+F4/80+ subset of CD11b+ cells was significantly increased. Because this subset also expressed the interleukin (IL)-4R and IL-10, we refer to these cells as “alternatively activated” or M2 macrophages. A greater percentage of M2 macrophages in Gdx males expressed the inhibitory receptor Tim-3, while fewer expressed IL-1β and IL-10. Only M2 macrophages upregulated TLR4 and Tim-3, whereas GR1−IL-4Rlo macrophages did not. Additionally, IL-4+CD4+ Th2 cells, Foxp3+ regulatory T (Treg) cells and Tim-3+CD4+ T cells were significantly increased in the heart following Gdx. Thus, we report for the first time that the inhibitory receptor Tim-3 is expressed on M2 macrophages. Our findings show that sex hormones and/ or other mediators released from the testes inhibit anti-inflammatory populations in the heart including Tim-3+ M2, Tim-3+CD4+ T cells, Th2 and Treg resulting in more severe acute cardiac inflammation in males following CVB3 infection.
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影响因子：
4.4
作者：
Fairweather, DeLisa;Frisancho-Kiss, Sylvia;Rose, Noel R.
通讯作者：
Rose, Noel R.
影响因子：
9.8
作者：
Feldman, Irv;Feldman, Gerald M.;Leslie, Kimberly K.
通讯作者：
Leslie, Kimberly K.
影响因子：
4.4
作者：
Frisancho-Kiss, Sylvia;Nyland, Jennifer F.;Fairweather, DeLisa
通讯作者：
Fairweather, DeLisa
影响因子：
4.4
作者：
Frisancho-Kiss, Sylvia;Davis, Sarah E.;Fairweather, DeLisa
通讯作者：
Fairweather, DeLisa
影响因子：
3.3
作者：
Chang, He;Hanawa, Haruo;Aizawa, Yoshifusa
通讯作者：
Aizawa, Yoshifusa