Cutting edge: Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease
Cutting edge: Cross-regulation by TLR4 and T cell Ig mucin-3 determines sex differences in inflammatory heart disease
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DOI：
10.4049/jimmunol.178.11.6710
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发表时间：
2007-06-01
影响因子：
4.4
通讯作者：
Fairweather, DeLisa
中科院分区：
文献类型：
--
作者：
Frisancho-Kiss, Sylvia;Davis, Sarah E.;Fairweather, DeLisa
最近的临床研究加强了心血管疾病发病机制中与性别有关的差异的重要性，男性的发病率和死亡率增加。与人类相似，感染柯萨奇病毒B3（CVB 3）的雄性BALB/c小鼠心脏会出现更严重的炎症，尽管病毒复制并不比雌性小鼠更严重。我们发现，TLR 4和IFN-γ水平显着升高和调节性T细胞（Treg）群体显着减少，在心脏的男性CVB 3感染后，而女性有显着增加的T细胞IG粘蛋白（Tim）-3，IL-4和Treg。在雄性中阻断Tim-3显著增加炎症和TLR 4表达，同时减少Treg。相反，缺陷的TLR 4信号传导显著减少炎症，同时增加Tim-3表达。TLR 4和Tim-3的交叉调节发生在先天性和适应性免疫应答期间。这种新的机制可能有助于解释为什么炎症性心脏病在男性中更严重。
Recent clinical studies have reinforced the importance of sex-related differences in the pathogenesis of cardiovascular diseases, with an increased incidence and mortality in men. Similar to humans, male BALB/c mice infected with coxsackievirus B3 (CVB3) develop more severe inflammation in the heart even though viral replication is no greater than in females. We show that TLR4 and IFN-gamma levels are significantly elevated and regulatory T cell (Treg) populations significantly reduced in the heart of males following CVB3 infection, whereas females have significantly increased T cell Ig mucin (Tim)-3, IL-4 and Treg. Blocking Tim-3 in males significantly increases inflammation and TLR4 expression while reducing Treg. In contrast, defective TLR4 signaling significantly reduces inflammation while increasing Tim-3 expression. Cross-regulation of TLR4 and Tim-3 occurs during the innate and adaptive immune response. This novel mechanism may help explain why inflammatory heart disease is more severe in males.