{"title":"HGF-DPSCs通过调节小鼠肺粘膜CCR1+ Th2细胞反应改善哮喘。","authors":"Geng Lin, Mengyu Tao, Heqiang Sun, Xinli Deng, Letong Zhang, Guixiang Sun, Yong Zhou, Guogang Xu","doi":"10.1016/j.jcyt.2025.02.005","DOIUrl":null,"url":null,"abstract":"<p><p>Asthma, a prevalent allergic disease affecting approximately 300 million individuals globally, remains a significant public health challenge. Mesenchymal stromal cells (MSCs) and hepatocyte growth factor (HGF), both recognized for their immunomodulatory properties, hold therapeutic potential for asthma. However, their precise mechanisms remain underexplored. The current study aimed to engineer human HGF overexpressing human dental pulp stromal cells (HGF-DPSCs) and evaluate their efficacy in asthma management while elucidating underlying mechanisms. The results showed that the constructed HGF-DPSCs overexpressed HGF both in vitro and in vivo. Also, compared with DPSCs, they demonstrated a more pronounced distribution within lung tissue. In house dust mite (HDM)-induced asthma, HGF-DPSCs showed a more significant inhibitory effect on airway hyperresponsiveness (AHR), inflammatory infiltration, and CD4<sup>+</sup> T-cell recruitment compared with DPSCs. Immunofluorescence analysis revealed a spatial overlap between HGF-DPSCs and pulmonary epithelial cells. Protein array analysis identified the chemokine Ckβ8-1 as a pivotal factor in the interaction between HGF-DPSCs and bronchial epithelial Beas-2B cells. Subsequent mechanistic investigations demonstrated that administration of HGF-DPSCs markedly reduced both the expression of Ckβ8-1 protein and the proportion of CD4<sup>+</sup>CCR1<sup>+</sup> T lymphocytes in the lungs of asthmatic mice. Furthermore, transwell migration assays incorporating a CKβ8-1 antagonist revealed a significant inhibition of CD4<sup>+</sup> T-cell migration. Flow cytometry analysis indicated that CD4<sup>+</sup>CCR1<sup>+</sup> T cells from the lungs of asthmatic mice exhibit a pronounced Th2 phenotype, characterized by high expression levels of IL-4, IL-5, and IL-13 cytokines. In conclusion, HGF-DPSCs ameliorate HDM-induced asthma by suppressing CCR1<sup>+</sup> Th2 cell responses via modulation of the Ckβ8-1/CCR1 axis, highlighting their potential as a novel therapeutic strategy.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HGF-DPSCs ameliorate asthma by regulating CCR1<sup>+</sup> Th2 cells responses in mice pulmonary mucosa.\",\"authors\":\"Geng Lin, Mengyu Tao, Heqiang Sun, Xinli Deng, Letong Zhang, Guixiang Sun, Yong Zhou, Guogang Xu\",\"doi\":\"10.1016/j.jcyt.2025.02.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Asthma, a prevalent allergic disease affecting approximately 300 million individuals globally, remains a significant public health challenge. Mesenchymal stromal cells (MSCs) and hepatocyte growth factor (HGF), both recognized for their immunomodulatory properties, hold therapeutic potential for asthma. However, their precise mechanisms remain underexplored. The current study aimed to engineer human HGF overexpressing human dental pulp stromal cells (HGF-DPSCs) and evaluate their efficacy in asthma management while elucidating underlying mechanisms. The results showed that the constructed HGF-DPSCs overexpressed HGF both in vitro and in vivo. Also, compared with DPSCs, they demonstrated a more pronounced distribution within lung tissue. In house dust mite (HDM)-induced asthma, HGF-DPSCs showed a more significant inhibitory effect on airway hyperresponsiveness (AHR), inflammatory infiltration, and CD4<sup>+</sup> T-cell recruitment compared with DPSCs. Immunofluorescence analysis revealed a spatial overlap between HGF-DPSCs and pulmonary epithelial cells. Protein array analysis identified the chemokine Ckβ8-1 as a pivotal factor in the interaction between HGF-DPSCs and bronchial epithelial Beas-2B cells. Subsequent mechanistic investigations demonstrated that administration of HGF-DPSCs markedly reduced both the expression of Ckβ8-1 protein and the proportion of CD4<sup>+</sup>CCR1<sup>+</sup> T lymphocytes in the lungs of asthmatic mice. Furthermore, transwell migration assays incorporating a CKβ8-1 antagonist revealed a significant inhibition of CD4<sup>+</sup> T-cell migration. Flow cytometry analysis indicated that CD4<sup>+</sup>CCR1<sup>+</sup> T cells from the lungs of asthmatic mice exhibit a pronounced Th2 phenotype, characterized by high expression levels of IL-4, IL-5, and IL-13 cytokines. In conclusion, HGF-DPSCs ameliorate HDM-induced asthma by suppressing CCR1<sup>+</sup> Th2 cell responses via modulation of the Ckβ8-1/CCR1 axis, highlighting their potential as a novel therapeutic strategy.</p>\",\"PeriodicalId\":50597,\"journal\":{\"name\":\"Cytotherapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-02-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cytotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jcyt.2025.02.005\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jcyt.2025.02.005","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
HGF-DPSCs ameliorate asthma by regulating CCR1+ Th2 cells responses in mice pulmonary mucosa.
Asthma, a prevalent allergic disease affecting approximately 300 million individuals globally, remains a significant public health challenge. Mesenchymal stromal cells (MSCs) and hepatocyte growth factor (HGF), both recognized for their immunomodulatory properties, hold therapeutic potential for asthma. However, their precise mechanisms remain underexplored. The current study aimed to engineer human HGF overexpressing human dental pulp stromal cells (HGF-DPSCs) and evaluate their efficacy in asthma management while elucidating underlying mechanisms. The results showed that the constructed HGF-DPSCs overexpressed HGF both in vitro and in vivo. Also, compared with DPSCs, they demonstrated a more pronounced distribution within lung tissue. In house dust mite (HDM)-induced asthma, HGF-DPSCs showed a more significant inhibitory effect on airway hyperresponsiveness (AHR), inflammatory infiltration, and CD4+ T-cell recruitment compared with DPSCs. Immunofluorescence analysis revealed a spatial overlap between HGF-DPSCs and pulmonary epithelial cells. Protein array analysis identified the chemokine Ckβ8-1 as a pivotal factor in the interaction between HGF-DPSCs and bronchial epithelial Beas-2B cells. Subsequent mechanistic investigations demonstrated that administration of HGF-DPSCs markedly reduced both the expression of Ckβ8-1 protein and the proportion of CD4+CCR1+ T lymphocytes in the lungs of asthmatic mice. Furthermore, transwell migration assays incorporating a CKβ8-1 antagonist revealed a significant inhibition of CD4+ T-cell migration. Flow cytometry analysis indicated that CD4+CCR1+ T cells from the lungs of asthmatic mice exhibit a pronounced Th2 phenotype, characterized by high expression levels of IL-4, IL-5, and IL-13 cytokines. In conclusion, HGF-DPSCs ameliorate HDM-induced asthma by suppressing CCR1+ Th2 cell responses via modulation of the Ckβ8-1/CCR1 axis, highlighting their potential as a novel therapeutic strategy.
期刊介绍：
The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.
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