Lipid-Sensing Receptor FFAR4 Modulates Pulmonary Epithelial Homeostasis following Immunogenic Exposures Independently of the FFAR4 Ligand Docosahexaenoic Acid (DHA).
Lipid-Sensing Receptor FFAR4 Modulates Pulmonary Epithelial Homeostasis following Immunogenic Exposures Independently of the FFAR4 Ligand Docosahexaenoic Acid (DHA).
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DOI：
10.3390/ijms24087072
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发表时间：
2023-04-11
影响因子：
5.6
通讯作者：
Nordgren, Tara M.
中科院分区：
文献类型：
--
作者：
Sveiven, Stefanie N.;Anesko, Kyle;Morgan, Joshua;Nair, Meera G.;Nordgren, Tara M.
肺游离脂肪酸受体4（FFAR 4）的作用尚未完全阐明，我们的目的是阐明FFAR 4对肺免疫应答和恢复稳态的影响。我们采用了一个已知的高风险的人肺免疫原性暴露于提取物的灰尘从猪圈养设施（DE）。WT和Ffar4缺失小鼠通过鼻内滴注重复暴露于DE，并通过口服管饲补充二十二碳六烯酸（DHA）。我们试图了解以前发现的DHA介导的DE诱导的炎症反应的衰减是否是FFAR 4依赖性的。我们发现DHA介导的抗炎作用独立于FFAR 4表达，并且缺乏FFAR 4的DE暴露小鼠气道中的免疫细胞减少，上皮发育不良，肺屏障完整性受损。使用免疫学基因表达面板对转录物的分析揭示了FFAR 4在肺中与炎症的先天免疫起始、细胞保护和免疫细胞迁移相关的作用。最终，FFAR 4在肺中的存在可以调节免疫损伤后的细胞存活和修复，提示肺部疾病的潜在治疗方向。
The role of pulmonary free fatty acid receptor 4 (FFAR4) is not fully elucidated and we aimed to clarify the impact of FFAR4 on the pulmonary immune response and return to homeostasis. We employed a known high-risk human pulmonary immunogenic exposure to extracts of dust from swine confinement facilities (DE). WT and Ffar4-null mice were repetitively exposed to DE via intranasal instillation and supplemented with docosahexaenoic acid (DHA) by oral gavage. We sought to understand if previous findings of DHA-mediated attenuation of the DE-induced inflammatory response are FFAR4-dependent. We identified that DHA mediates anti-inflammatory effects independent of FFAR4 expression, and that DE-exposed mice lacking FFAR4 had reduced immune cells in the airways, epithelial dysplasia, and impaired pulmonary barrier integrity. Analysis of transcripts using an immunology gene expression panel revealed a role for FFAR4 in lungs related to innate immune initiation of inflammation, cytoprotection, and immune cell migration. Ultimately, the presence of FFAR4 in the lung may regulate cell survival and repair following immune injury, suggestive of potential therapeutic directions for pulmonary disease.
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影响因子：
5.6
作者：
Ichimura A;Hasegawa S;Kasubuchi M;Kimura I
通讯作者：
Kimura I
影响因子：
5.5
作者：
Batugedara, Hashini M.;Li, Jiang;Nair, Meera G.
通讯作者：
Nair, Meera G.
DOI：
10.1155/2013/191823
发表时间：
2013-05-12
期刊：
ISRN inflammation
影响因子：
--
作者：
Dessì M;Noce A;Bertucci P;Manca di Villahermosa S;Zenobi R;Castagnola V;Addessi E;Di Daniele N
通讯作者：
Di Daniele N
DOI：
10.1038/nrd.2017.178
发表时间：
2017-12
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Hauser AS;Attwood MM;Rask-Andersen M;Schiöth HB;Gloriam DE
通讯作者：
Gloriam DE
影响因子：
3.7
作者：
Kim SY;Barnes MA;Sureshchandra S;Menicucci AR;Patel JJ;Messaoudi I;Nair MG
通讯作者：
Nair MG