BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages
Abstract Alternatively activated M2-like macrophages have a profound impact on asthma pathogenesis. Basic Helix-Loop-Helix Family Member E40 (BHLHE40), a dimeric transcriptional factor, plays a key regulation in macrophage functions. Here we show that ovalbumin (OVA)-challenged mice exhibited greate...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08288-1 |
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| author | Bing Dai Li Chen Xiaowen Li Qianlan Zhou Qinzhen Zhang Lina Han Wenxin Shen Qing Chang Yuhong Zhao Si Liu Lishen Shan |
| author_facet | Bing Dai Li Chen Xiaowen Li Qianlan Zhou Qinzhen Zhang Lina Han Wenxin Shen Qing Chang Yuhong Zhao Si Liu Lishen Shan |
| author_sort | Bing Dai |
| collection | DOAJ |
| description | Abstract Alternatively activated M2-like macrophages have a profound impact on asthma pathogenesis. Basic Helix-Loop-Helix Family Member E40 (BHLHE40), a dimeric transcriptional factor, plays a key regulation in macrophage functions. Here we show that ovalbumin (OVA)-challenged mice exhibited greater expression of BHLHE40 in lung tissues. Bhlhe40 knockdown reduced the pulmonary lesions and allergy-induced inflammation in asthmatic mice. Moreover, an inhibitory effect of Bhlhe40 knockdown on alternative activation was observed in vivo and in vitro. We show a downstream target Neurturin (Nrtn) of Bhlhe40. Dual luciferase assay and ChIP-qPCR assay indicated that BHLHE40 bound to Nrtn promoter and reduced its transcriptional activity. Simultaneous knockdown of Bhlhe40 and Nrtn recovered the alternative activation of macrophages and rescued the OVA-elicited asthma phenotype. NRTN downregulation offset the alleviative effects of Bhlhe40 knockdown on asthma. This study demonstrates that BHLHE40 promotes allergic asthma, and contributes to the alternative activation of macrophages in asthma by inhibiting Nrtn transcription. |
| format | Article |
| id | doaj-art-101174fa397f45fda571c50bbcf8cd78 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-101174fa397f45fda571c50bbcf8cd782025-08-20T03:25:19ZengNature PortfolioCommunications Biology2399-36422025-06-018111510.1038/s42003-025-08288-1BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophagesBing Dai0Li Chen1Xiaowen Li2Qianlan Zhou3Qinzhen Zhang4Lina Han5Wenxin Shen6Qing Chang7Yuhong Zhao8Si Liu9Lishen Shan10Department of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityLiaoning Key Laboratory of Precision Medical Research on Major Chronic Disease, Clinical Research Center of Shengjing Hospital of China Medical UniversityDepartment of Clinical Epidemiology, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityDepartment of Pediatrics, Shengjing Hospital of China Medical UniversityAbstract Alternatively activated M2-like macrophages have a profound impact on asthma pathogenesis. Basic Helix-Loop-Helix Family Member E40 (BHLHE40), a dimeric transcriptional factor, plays a key regulation in macrophage functions. Here we show that ovalbumin (OVA)-challenged mice exhibited greater expression of BHLHE40 in lung tissues. Bhlhe40 knockdown reduced the pulmonary lesions and allergy-induced inflammation in asthmatic mice. Moreover, an inhibitory effect of Bhlhe40 knockdown on alternative activation was observed in vivo and in vitro. We show a downstream target Neurturin (Nrtn) of Bhlhe40. Dual luciferase assay and ChIP-qPCR assay indicated that BHLHE40 bound to Nrtn promoter and reduced its transcriptional activity. Simultaneous knockdown of Bhlhe40 and Nrtn recovered the alternative activation of macrophages and rescued the OVA-elicited asthma phenotype. NRTN downregulation offset the alleviative effects of Bhlhe40 knockdown on asthma. This study demonstrates that BHLHE40 promotes allergic asthma, and contributes to the alternative activation of macrophages in asthma by inhibiting Nrtn transcription.https://doi.org/10.1038/s42003-025-08288-1 |
| spellingShingle | Bing Dai Li Chen Xiaowen Li Qianlan Zhou Qinzhen Zhang Lina Han Wenxin Shen Qing Chang Yuhong Zhao Si Liu Lishen Shan BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages Communications Biology |
| title | BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages |
| title_full | BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages |
| title_fullStr | BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages |
| title_full_unstemmed | BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages |
| title_short | BHLHE40 contributes to allergic asthma progression in mice through NRTN downregulation in macrophages |
| title_sort | bhlhe40 contributes to allergic asthma progression in mice through nrtn downregulation in macrophages |
| url | https://doi.org/10.1038/s42003-025-08288-1 |
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