lincRNA-Cox2 Functions to Regulate Inflammation in Alveolar Macrophages during Acute Lung Injury.
lincRNA-Cox2 Functions to Regulate Inflammation in Alveolar Macrophages during Acute Lung Injury.
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DOI：
10.4049/jimmunol.2100743
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发表时间：
2022-04-15
影响因子：
4.4
通讯作者：
Carpenter, Susan
中科院分区：
文献类型：
--
作者：
Robinson, Elektra Kantzari;Worthington, Atesh;Poscablo, Donna;Shapleigh, Barbara;Salih, Mays Mohammed;Halasz, Haley;Seninge, Lucas;Mosqueira, Benny;Smaliy, Valeriya;Forsberg, E. Camilla;Carpenter, Susan
呼吸系统存在于我们的身体和周围非无菌环境之间的界面;因此，通过炎症线索的平衡来维持稳态是至关重要的。适当的炎症反应对于对抗病原体至关重要，而过度或不受控制的反应可能导致慢性疾病的发展。最近的研究表明，基因组的活跃转录非编码区正在成为包括炎症在内的生物过程的关键调节因子。LincRNA-Cox 2是一种炎症诱导型长基因间非编码RNA，其功能是微调免疫基因表达。在这里，除了荧光激活的细胞分选之外，我们还使用批量和单细胞RNA-seq鉴定了lincRNA-Cox 2在肺中表达最高，特别是在肺泡巨噬细胞中，其功能是调节急性炎症途径。虽然我们以前报道，lincRNA-Cox 2可以发挥作用，以调节其邻近基因Ptgs 2顺式，在这里，我们使用遗传小鼠模型，以确认其在调节基因表达的作用更广泛的反式。我们确定的基因，包括Ccl 3，Ccl 4和Ccl 5在lincRNA-Cox 2缺陷小鼠失调。通过将缺陷小鼠与我们新产生的lincRNA-Cox 2转基因小鼠杂交，这些基因都被拯救回野生型水平，证实了该基因的反式功能。我们证实，这些基因中的许多基因在起源于骨髓的肺泡巨噬细胞内受到特异性调节，因为可以通过将野生型骨髓移植到lincRNA-Cox 2缺陷小鼠中来逆转表型。这项工作极大地扩展了我们对lincRNA-Cox 2在宿主防御中的作用的理解，并突出了它在肺泡巨噬细胞中调节肺内免疫反应的重要作用。
The respiratory system exists at the interface between our body and the surrounding non-sterile environment; therefore, it is critical for a state of homeostasis to be maintained through a balance of inflammatory cues. An appropriate inflammatory response is vital for combating pathogens, while an excessive or uncontrolled response can lead to the development of chronic disease. Recent studies have shown that actively transcribed noncoding regions of the genome are emerging as key regulators of biological processes, including inflammation. LincRNA-Cox2 is one such example of an inflammatory inducible long intergenic noncoding RNA functioning to fine tune immune gene expression. Here using bulk and single-cell RNA-seq, in addition to fluorescence activated cell sorting, we identify that lincRNA-Cox2 is most highly expressed in the lung, particularly in alveolar macrophages where it functions to regulate the acute inflammatory pathway. While we previously reported that lincRNA-Cox2 can function to regulate its neighboring gene Ptgs2 in cis, here we use genetic mouse models to confirm its role in regulating gene expression more broadly in trans. We identify genes including Ccl3, Ccl4 and Ccl5 that are dysregulated in lincRNA-Cox2 deficient mice. These genes are all rescued back to wild type levels by crossing the deficient mice with our newly generated lincRNA-Cox2 transgenic mice confirming that this gene functions in trans. We confirm that many of these genes are specifically regulated within alveolar macrophages that originate in the bone marrow as the phenotype can be reversed by transplantation of wild type bone marrow into the lincRNA-Cox2 deficient mice. This work greatly expands our understanding of the role for lincRNA-Cox2 in host defense and highlights the important role it plays in alveolar macrophages to regulate immune responses within the lung.
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影响因子：
5.8
作者：
Nolan A;Kwon S;Cho SJ;Naveed B;Comfort AL;Prezant DJ;Rom WN;Weiden MD
通讯作者：
Weiden MD
影响因子：
82.9
作者：
Cloonan SM;Glass K;Laucho-Contreras ME;Bhashyam AR;Cervo M;Pabón MA;Konrad C;Polverino F;Siempos II;Perez E;Mizumura K;Ghosh MC;Parameswaran H;Williams NC;Rooney KT;Chen ZH;Goldklang MP;Yuan GC;Moore SC;Demeo DL;Rouault TA;D'Armiento JM;Schon EA;Manfredi G;Quackenbush J;Mahmood A;Silverman EK;Owen CA;Choi AM
通讯作者：
Choi AM
影响因子：
3
作者：
Bonville CA;Percopo CM;Dyer KD;Gao J;Prussin C;Foster B;Rosenberg HF;Domachowske JB
通讯作者：
Domachowske JB
DOI：
10.1126/science.1240925
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carpenter S;Aiello D;Atianand MK;Ricci EP;Gandhi P;Hall LL;Byron M;Monks B;Henry-Bezy M;Lawrence JB;O'Neill LA;Moore MJ;Caffrey DR;Fitzgerald KA
通讯作者：
Fitzgerald KA
影响因子：
4.6
作者：
Gangwar, Roopesh Singh;Vinayachandran, Vinesh;Rajagopalan, Sanjay
通讯作者：
Rajagopalan, Sanjay