The Heterogeneity of Ly6C(hi) Monocytes Controls Their Differentiation into iNOS(+) Macrophages or Monocyte-Derived Dendritic Cells.
The Heterogeneity of Ly6C(hi) Monocytes Controls Their Differentiation into iNOS(+) Macrophages or Monocyte-Derived Dendritic Cells.
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DOI：
10.1016/j.immuni.2016.12.001
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发表时间：
2016-12-20
期刊：
影响因子：
32.4
通讯作者：
Guermonprez, Pierre
中科院分区：
文献类型：
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作者：
Menezes, Shinelle;Melandri, Daisy;Anselmi, Giorgio;Perchet, Thibaut;Loschko, Jakob;Dubrot, Juan;Patel, Rajen;Gautier, Emmanuel L.;Hugues, Stephanie;Longhi, M. Paula;Henry, Jake Y.;Quezada, Sergio A.;Lauvau, Gregoire;Lennon-Dumenil, Ana-Maria;Gutierrez-Martinez, Enrique;Bessis, Alain;Gomez-Perdiguero, Elisa;Jacome-Galarza, Christian E.;Garner, Hannah;Geissmann, Frederic;Golub, Rachel;Nussenzweig, Michel C.;Guermonprez, Pierre
炎症触发Ly 6Chi单核细胞分化成杀微生物巨噬细胞或单核细胞衍生的树突状细胞（moDC）。然而，目前尚不清楚是否环境炎症线索控制单核细胞的极化向这些命运或是否专门的单核细胞祖细胞亚群存在炎症前。在这里，我们已经表明，幼稚单核细胞是表型异质性，并包含NR 4A 1-和Flt 3L-独立，CCR 2-依赖，Flt 3 + CD 11 c −MHCII+PU.1hi子集。该亚群作为FcγRIII+PD-L2+ CD 209 a+、GM-CSF依赖性moDC的前体，但远离DC谱系，如使用Zbtb 46的命运作图实验所示。相比之下，Flt 3 − CD 11 c −MHCII−PU.1lo单核细胞在微生物刺激下分化为FcγRIII+PD-L2− CD 209 a −iNOS+巨噬细胞。重要的是，Sfpi 1单倍不足在遗传上区分了单核细胞对moDCs或杀微生物巨噬细胞的前体活性。事实上，Sfpi 1 +/−小鼠的Flt 3 + CD 11 c −MHCII+单核细胞和GM-CSF依赖性FcγRIII+PD-L2+ CD 209 a + moDCs减少，但产生iNOS+巨噬细胞的效率更高。因此，幼稚单核细胞内PU. 1表达的细胞间差异分离炎性iNOS+巨噬细胞或moDC的祖细胞活性。小鼠Ly 6ChiCD 115+单核细胞是异质性DC相关基因（Cd 209 a和MHCII）在FcγRIII+单核细胞亚群中表达GM-CSF依赖性CD 209 a + moDC由Fcγ RIII+ CD 209 a +MHCII+单核细胞产生iNOS+巨噬细胞由FcγRIII+ CD 209 a −MHCII−单核细胞产生单核细胞在炎症过程中可以分化为多个后代。在这里，梅内塞斯等人。显示来自幼稚小鼠的单核细胞是异质的，并且含有不同的前体亚群，其产生iNOS+炎性巨噬细胞或GM-CSF诱导的CD 209 a+单核细胞衍生的树突细胞。
Inflammation triggers the differentiation of Ly6Chi monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3+CD11c−MHCII+PU.1hi subset. This subset acted as a precursor for FcγRIII+PD-L2+CD209a+, GM-CSF-dependent moDCs but was distal from the DC lineage, as shown by fate-mapping experiments using Zbtb46. By contrast, Flt3−CD11c−MHCII−PU.1lo monocytes differentiated into FcγRIII+PD-L2−CD209a−iNOS+ macrophages upon microbial stimulation. Importantly, Sfpi1 haploinsufficiency genetically distinguished the precursor activities of monocytes toward moDCs or microbicidal macrophages. Indeed, Sfpi1+/− mice had reduced Flt3+CD11c−MHCII+ monocytes and GM-CSF-dependent FcγRIII+PD-L2+CD209a+ moDCs but generated iNOS+ macrophages more efficiently. Therefore, intercellular disparities of PU.1 expression within naive monocytes segregate progenitor activity for inflammatory iNOS+ macrophages or moDCs. Murine Ly6ChiCD115+ monocytes are heterogeneous DC-related genes (Cd209a and MHCII) are expressed in a subset of FcγRIII+ monocytes GM-CSF-dependent CD209a+ moDCs are generated by FcγRIII+CD209a+MHCII+ monocytes iNOS+ macrophages are generated by FcγRIII+CD209a−MHCII− monocytes Monocytes can differentiate into multiple progenies during inflammation. Here, Menezes et al. show that monocytes from naive mice are heterogeneous and contain distinct precursor subsets giving rise to iNOS+ inflammatory macrophages or GM-CSF-induced CD209a+ monocyte-derived dendritic cells.
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DOI：
10.1084/jem.20050075
发表时间：
2005-05-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dakic A;Metcalf D;Di Rago L;Mifsud S;Wu L;Nutt SL
通讯作者：
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影响因子：
11.4
作者：
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影响因子：
30.5
作者：
通讯作者：
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DOI：
10.1084/jem.20141441
发表时间：
2015-03-09
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Breton G;Lee J;Zhou YJ;Schreiber JJ;Keler T;Puhr S;Anandasabapathy N;Schlesinger S;Caskey M;Liu K;Nussenzweig MC
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影响因子：
4.4
作者：
Jurkin, Jennifer;Schichl, Yvonne M.;Strobl, Herbert
通讯作者：
Strobl, Herbert