IRF5 guides monocytes toward an inflammatory CD11c(+) macrophage phenotype and promotes intestinal inflammation.
IRF5 guides monocytes toward an inflammatory CD11c(+) macrophage phenotype and promotes intestinal inflammation.
复制标题
DOI：
10.1126/sciimmunol.aax6085
复制
发表时间：
2020-05-22
影响因子：
24.8
通讯作者：
Udalova IA
中科院分区：
文献类型：
--
作者：
Corbin AL;Gomez-Vazquez M;Berthold DL;Attar M;Arnold IC;Powrie FM;Sansom SN;Udalova IA
单核吞噬细胞（MNPs）对于维持肠道内稳态至关重要，但在急性微生物刺激下也会引发免疫病理，加速Ly6Chi单核细胞向肠道的募集。控制肠道单核细胞组织适应的调节因子仍然知之甚少。干扰素调节因子5 （IRF5）是一种转录因子，在维持巨噬细胞的炎症表型中发挥关键作用。在这里，我们研究了IRF5在稳态和炎症期间对肠道MNP系统和生理的影响。我们证明，在稳定状态下，IRF5缺乏对结肠生理的影响有限，但改善了肝螺杆菌诱导结肠炎期间的免疫病理。IRF5活性在MNPs表型中的抑制反映了全球IRF5缺陷。利用骨髓嵌合体和单细胞rna测序方法的结合，我们研究了IRF5在控制结肠MNP发育中的内在作用。我们证明IRF5促进Ly6Chi单核细胞向CD11c+巨噬细胞的分化，并控制这些细胞抗微生物和炎症介质的产生。因此，我们确定IRF5是肠道炎症期间结肠MNP系统的关键转录调节因子。
Mononuclear phagocytes (MNPs) are vital for maintaining intestinal homeostasis but in response to acute microbial stimulation can also trigger immunopathology, accelerating recruitment of Ly6Chi monocytes to the gut. The regulators that control monocyte tissue adaptation in the gut remain poorly understood. Interferon Regulatory Factor 5 (IRF5) is a transcription factor previously shown to play a key role in maintaining the inflammatory phenotype of macrophages. Here we investigate the impact of IRF5 on the MNP system and physiology of the gut at homeostasis and during inflammation. We demonstrate that IRF5 deficiency has a limited impact on colon physiology at steady state but ameliorates immunopathology during Helicobacter hepaticus induced colitis. Inhibition of IRF5 activity in MNPs phenocopies global IRF5 deficiency. Using a combination of bone marrow chimera and single cell RNA-sequencing approaches we examined the intrinsic role of IRF5 in controlling colonic MNP development. We demonstrate that IRF5 promotes differentiation of Ly6Chi monocytes into CD11c+ macrophages and controls the production of anti-microbial and inflammatory mediators by these cells. Thus, we identify IRF5 as a key transcriptional regulator of the colonic MNP system during intestinal inflammation.
登录
查看更多内容
影响因子：
5.6
作者：
Jha P;Das H
通讯作者：
Das H
DOI：
10.1084/jem.20170057
发表时间：
2018-02-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bujko A;Atlasy N;Landsverk OJB;Richter L;Yaqub S;Horneland R;Øyen O;Aandahl EM;Aabakken L;Stunnenberg HG;Bækkevold ES;Jahnsen FL
通讯作者：
Jahnsen FL
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1084/jem.20111453
发表时间：
2012-08-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coccia M;Harrison OJ;Schiering C;Asquith MJ;Becher B;Powrie F;Maloy KJ
通讯作者：
Maloy KJ
影响因子：
16.6
作者：
Asano K;Takahashi N;Ushiki M;Monya M;Aihara F;Kuboki E;Moriyama S;Iida M;Kitamura H;Qiu CH;Watanabe T;Tanaka M
通讯作者：
Tanaka M