Regulation of monocyte functional heterogeneity by miR-146a and Relb.
Regulation of monocyte functional heterogeneity by miR-146a and Relb.
复制标题
DOI：
10.1016/j.celrep.2012.02.009
复制
发表时间：
2012-04-19
期刊：
影响因子：
8.8
通讯作者：
Pittet MJ
中科院分区：
文献类型：
--
作者：
Etzrodt M;Cortez-Retamozo V;Newton A;Zhao J;Ng A;Wildgruber M;Romero P;Wurdinger T;Xavier R;Geissmann F;Meylan E;Nahrendorf M;Swirski FK;Baltimore D;Weissleder R;Pittet MJ
单核细胞是抵抗感染和损伤的中央防御系统，但也可以促进病理性炎症反应。考虑到单核细胞存在于至少两个致力于不同功能的亚群中的证据，我们调查了体内不同因素是否调节单核细胞亚群反应之间的平衡。我们鉴定了一种microRNA(MiRNA)miR-146a，它在小鼠(Ly-6chi/Ly-6Clo)和人(CD14hi/CD14loCD16+)单核细胞亚群中都有差异调控。单个miRNA在炎症刺激过程中控制Ly-6chi单核细胞反应的幅度，但不影响Ly-6Clo细胞。MIR-146a介导的调节是细胞内的，依赖于非典范的NF-κB/REL家族成员Relb，我们确定它是miR-146a的直接靶标。这些观察不仅为调节由承诺的单核细胞前体群体介导的反应的分子事件提供了新的机制见解，而且还识别了新的靶点来操纵Ly-6chi单核细胞的反应，同时抑制Ly-6Clo单核细胞的活性。
Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6Chi/Ly-6Clo) and human (CD14hi/CD14loCD16+) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6Chi monocyte response during inflammatory challenge whereas it did not affect Ly-6Clo cells. miR-146a–mediated regulation was cell-intrinsic and depended on Relb, a member of the non-canonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide novel mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify novel targets to manipulate Ly-6Chi monocyte responses while sparing Ly-6Clo monocyte activity.
登录
查看更多内容
影响因子：
32.4
作者：
Wu, L;D'Amico, A;Shortman, K
通讯作者：
Shortman, K
影响因子：
11.2
作者：
Movahedi, Kiavash;Laoui, Damya;Van Ginderachter, Jo A.
通讯作者：
Van Ginderachter, Jo A.
影响因子：
56.9
作者：
Farh, KKH;Grimson, A;Bartel, DP
通讯作者：
Bartel, DP
DOI：
10.1038/nri3070
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0708576105
发表时间：
2008-03-11
影响因子：
11.1
作者：
Vaira, Sergio;Johnson, Trevor;Novack, Deborah Veis
通讯作者：
Novack, Deborah Veis