The myeloid type I interferon response to myocardial infarction begins in bone marrow and is regulated by Nrf2-activated macrophages.
The myeloid type I interferon response to myocardial infarction begins in bone marrow and is regulated by Nrf2-activated macrophages.
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DOI：
10.1126/sciimmunol.aaz1974
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发表时间：
2020-09-25
影响因子：
24.8
通讯作者：
King KR
中科院分区：
文献类型：
--
作者：
Calcagno DM;Ng RP Jr;Toomu A;Zhang C;Huang K;Aguirre AD;Weissleder R;Daniels LB;Fu Z;King KR
无菌组织损伤被认为是通过损伤相关分子模式（DAMP）局部激活先天免疫反应。先天免疫通路是否被远程激活仍然相对未被探索。在这里，通过分析小鼠和人类在稳态和心肌梗死（MI）后的约145，000个单细胞转录组，我们表明I型干扰素（IFN）反应，其特征在于干扰素刺激基因（ISG）的表达，开始远离损伤部位，在骨髓内的中性粒细胞和单核细胞祖细胞中。在患者的外周血中，我们观察到表达ISG的中性粒细胞和单核细胞的定义子集。在小鼠的骨髓和血液中，在中性粒细胞和单核细胞及其祖细胞中检测到ISG表达;在稳态和MI后随着成熟而增强;并且由Tet 2和Irf 3转录调节因子控制。在梗死心脏内，ISG表达细胞受到Ccr 2 −稳态心脏巨噬细胞中Nrf 2激活的负调控。我们的研究结果表明，IFN信号开始于骨髓，涉及多种转录调节因子（Tet 2，Irf 3，Nrf 2）在管理ISG的表达，并提供了一个临床生物标志物（ISG评分）研究IFN信号在患者。
Sterile tissue injury is thought to locally activate innate immune responses via damage associated molecular patterns (DAMPs). Whether innate immune pathways are remotely activated remains relatively unexplored. Here, by analyzing ~145,000 single cell transcriptomes at steady state and after myocardial infarction (MI) in mice and humans, we show that the type I interferon (IFN) response, characterized by expression of interferon-stimulated genes (ISGs), begins far from the site of injury, in neutrophil and monocyte progenitors within the bone marrow. In the peripheral blood of patients, we observed defined subsets of ISG-expressing neutrophils and monocytes. In the bone marrow and blood of mice, ISG expression was detected in neutrophils and monocytes and their progenitors; intensified with maturation at steady-state and after MI; and was controlled by Tet2 and Irf3 transcriptional regulators. Within the infarcted heart, ISG-expressing cells were negatively regulated by Nrf2 activation in Ccr2− steady-state cardiac macrophages. Our results show that IFN signaling begins in the bone marrow, implicate multiple transcriptional regulators (Tet2, Irf3, Nrf2) in governing ISG expression, and provide a clinical biomarker (ISG score) for studying IFN signaling in patients.
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IRF3和I型干扰物为心肌梗死提供了致命的反应。
影响因子：
82.9
作者：
King KR;Aguirre AD;Ye YX;Sun Y;Roh JD;Ng RP Jr;Kohler RH;Arlauckas SP;Iwamoto Y;Savol A;Sadreyev RI;Kelly M;Fitzgibbons TP;Fitzgerald KA;Mitchison T;Libby P;Nahrendorf M;Weissleder R
通讯作者：
Weissleder R
影响因子：
30.5
作者：
Dick, Sarah A.;Macklin, Jillian A.;Epelman, Slava
通讯作者：
Epelman, Slava
影响因子：
64.8
作者：
Hérault A;Binnewies M;Leong S;Calero-Nieto FJ;Zhang SY;Kang YA;Wang X;Pietras EM;Chu SH;Barry-Holson K;Armstrong S;Göttgens B;Passegué E
通讯作者：
Passegué E
DOI：
10.1056/nejmoa1701719
发表时间：
2017-07-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Jaiswal S;Natarajan P;Silver AJ;Gibson CJ;Bick AG;Shvartz E;McConkey M;Gupta N;Gabriel S;Ardissino D;Baber U;Mehran R;Fuster V;Danesh J;Frossard P;Saleheen D;Melander O;Sukhova GK;Neuberg D;Libby P;Kathiresan S;Ebert BL
通讯作者：
Ebert BL
DOI：
10.1126/science.aal5081
发表时间：
2017-12-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Engblom C;Pfirschke C;Zilionis R;Da Silva Martins J;Bos SA;Courties G;Rickelt S;Severe N;Baryawno N;Faget J;Savova V;Zemmour D;Kline J;Siwicki M;Garris C;Pucci F;Liao HW;Lin YJ;Newton A;Yaghi OK;Iwamoto Y;Tricot B;Wojtkiewicz GR;Nahrendorf M;Cortez-Retamozo V;Meylan E;Hynes RO;Demay M;Klein A;Bredella MA;Scadden DT;Weissleder R;Pittet MJ
通讯作者：
Pittet MJ