The miR-23a∼27a∼24-2 microRNA Cluster Promotes Inflammatory Polarization of Macrophages.
The miR-23a∼27a∼24-2 microRNA Cluster Promotes Inflammatory Polarization of Macrophages.
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miR-23a〜27a〜24-2 microRNA簇促进巨噬细胞的炎症极化。
DOI：
10.4049/jimmunol.1901277
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发表时间：
2021-02-01
期刊：
影响因子：
--
通讯作者：
Dahl R
中科院分区：
文献类型：
--
作者：
Boucher A;Klopfenstein N;Hallas WM;Skibbe J;Appert A;Jang SH;Pulakanti K;Rao S;Cowden Dahl KD;Dahl R
巨噬细胞对调节炎症反应至关重要。环境信号使巨噬细胞进入促炎（M1）状态或抗炎（M2）状态。我们观察到microRNA簇mirn 23 a，编码miRs-23 a ~ 27 a ~24-2，调节小鼠巨噬细胞极化。对mirn 23 a缺陷型髓系祖细胞的基因表达分析显示Toll样受体和干扰素信号传导减少。Mirn 23 a −/−骨髓源性巨噬细胞（BMDM）对脂多糖（LPS）的反应减弱，表明成熟细胞具有抗炎表型。在体外，mirn 23 a −/− BMDM具有降低的M1反应和增强的M2反应。过表达mirn 23 a具有相反的作用，增强M1和抑制M2基因表达。有趣的是，mirn 23 a miRNAs的表达随着炎症刺激而下降，随着抗炎刺激而上升，这表明其调节防止将巨噬细胞锁定在极化状态。肿瘤相关巨噬细胞（TAM）的M2极化与许多肿瘤的不良结局相关，因此为了确定mirn 23 a缺失是否具有调节免疫细胞极化的功能性后果，我们测定了野生型和mirn 23 a −/−小鼠中的同基因肿瘤生长。与体外增加的抗炎/免疫抑制表型一致，与野生型小鼠相比，接种同基因肿瘤细胞的mirn 23 a −/−小鼠的结果更差。将肿瘤细胞与mirn 23 a −/− BMDM共注射到野生型小鼠中，表型模拟了mirn 23 a −/−小鼠中的肿瘤生长，这支持了mirn 23 a miRNA在巨噬细胞介导的肿瘤免疫中的关键作用。我们的数据表明，mirn 23 a调节M1/M2极化，并表明操纵mirn 23 a miRNA可用于指导巨噬细胞极化以驱动所需的免疫应答。
Macrophages are critical for regulating inflammatory responses. Environmental signals polarize macrophages to either a pro-inflammatory (M1) state or an anti-inflammatory (M2) state. We observed that the microRNA cluster mirn23a, coding for miRs-23a~27a~24–2, regulates mouse macrophage polarization. Gene expression analysis of mirn23a deficient myeloid progenitors revealed a decrease in Toll like receptor and interferon signaling. Mirn23a−/− bone marrow derived macrophages (BMDMs) have an attenuated response to lipopolysaccharide (LPS) demonstrating an anti-inflammatory phenotype in mature cells. In vitro, mirn23a−/− BMDMs have decreased M1 responses and an enhanced M2 responses. Overexpression of mirn23a has the opposite effect enhancing M1 and inhibiting M2 gene expression. Interestingly expression of mirn23a miRNAs goes down with inflammatory stimulation and up with anti-inflammatory stimulation suggesting that its regulation prevents locking macrophages into polarized states. M2 polarization of tumor associated macrophages (TAMs) correlates with poor outcome for many tumors, so to determine if there was a functional consequence of mirn23a loss modulating immune cell polarization we assayed syngeneic tumor growth in wildtype and mirn23a−/− mice. Consistent with the increased anti-inflammatory/ immunosuppressive phenotype in vitro, mirn23a−/− mice inoculated with syngeneic tumor cells had worse outcomes compared to wildtype mice. Co-injecting tumor cells with mirn23a−/− BMDMs into wildtype mice phenocopied tumor growth in mirn23a−/− mice supporting a critical role for mirn23a miRNAs in macrophage mediated tumor immunity. Our data demonstrates that mirn23a regulates M1/M2 polarization and suggests that manipulation of mirn23a miRNA can be used to direct macrophage polarization to drive a desired immune response.
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影响因子：
3.7
作者：
Jablonski KA;Amici SA;Webb LM;Ruiz-Rosado Jde D;Popovich PG;Partida-Sanchez S;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
影响因子：
3.1
作者：
AMANO, F;AKAMATSU, Y
通讯作者：
AKAMATSU, Y
影响因子：
2.6
作者：
Kong, Kimi Y.;Owens, Kristin S.;Rogers, Jason H.;Mullenix, Jason;Velu, Chinavenmeni S.;Grimes, H. Leighton;Dahl, Richard
通讯作者：
Dahl, Richard
影响因子：
30.5
作者：
Boone, DL;Turer, EE;Ma, A
通讯作者：
Ma, A
影响因子：
64.8
作者：
Kruidenier L;Chung CW;Cheng Z;Liddle J;Che K;Joberty G;Bantscheff M;Bountra C;Bridges A;Diallo H;Eberhard D;Hutchinson S;Jones E;Katso R;Leveridge M;Mander PK;Mosley J;Ramirez-Molina C;Rowland P;Schofield CJ;Sheppard RJ;Smith JE;Swales C;Tanner R;Thomas P;Tumber A;Drewes G;Oppermann U;Patel DJ;Lee K;Wilson DM
通讯作者：
Wilson DM