The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model
In our previous study, we revealed the ameliorative therapeutic effect of dexamethasone (Dex) for Lupus nephritis lesions in the MRL/MpJ-<i>Fas <sup>lpr/lpr</sup></i> (Lpr) mouse model. The female Lpr mice developed a greater number of mediastinal fat-associated lymphoid clus...
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2022-04-01
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| Online Access: | https://www.mdpi.com/1422-0067/23/8/4449 |
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| author | Yaser Hosny Ali Elewa Md Abdul Masum Sherif Kh. A. Mohamed Md Rashedul Islam Teppei Nakamura Osamu Ichii Yasuhiro Kon |
| author_facet | Yaser Hosny Ali Elewa Md Abdul Masum Sherif Kh. A. Mohamed Md Rashedul Islam Teppei Nakamura Osamu Ichii Yasuhiro Kon |
| author_sort | Yaser Hosny Ali Elewa |
| collection | DOAJ |
| description | In our previous study, we revealed the ameliorative therapeutic effect of dexamethasone (Dex) for Lupus nephritis lesions in the MRL/MpJ-<i>Fas <sup>lpr/lpr</sup></i> (Lpr) mouse model. The female Lpr mice developed a greater number of mediastinal fat-associated lymphoid clusters (MFALCs) and inflammatory lung lesions compared to the male mice. However, the effect of Dex, an immunosuppressive drug, on both lung lesions and the development of MFALCs in Lpr mice has not been identified yet. Therefore, in this study, we compared the development of lung lesions and MFALCs in female Lpr mice that received either saline (saline group “SG”) or dexamethasone (dexamethasone group “DG”) in drinking water as a daily dose along with weekly intraperitoneal injections for 10 weeks. Compared to the SG group, the DG group showed a significant reduction in the levels of serum anti-dsDNA antibodies, the size of MFALCs, the degree of lung injury, the area of high endothelial venules (HEVs), and the number of proliferating and immune cells in both MFALCs and the lungs. A significant positive correlation was observed between the size of MFALCs and the cellular aggregation in the lungs of Lpr mice. Therefore, this study confirmed the ameliorative effect of Dex on the development of lung injury and MFALCs via their regressive effect on both immune cells’ proliferative activity and the development of HEVs. Furthermore, the reprogramming of MFALCs by targeting immune cells and HEVs may provide a therapeutic strategy for autoimmune-disease-associated lung injury. |
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| language | English |
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| publishDate | 2022-04-01 |
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| spelling | doaj.art-055136f12ea1499084a96b9e0a556db22023-12-01T21:04:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238444910.3390/ijms23084449The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse ModelYaser Hosny Ali Elewa0Md Abdul Masum1Sherif Kh. A. Mohamed2Md Rashedul Islam3Teppei Nakamura4Osamu Ichii5Yasuhiro Kon6Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, JapanLaboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, JapanDepartment of Anatomy and Embryology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, EgyptLaboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, JapanLaboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, JapanLaboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, JapanLaboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, JapanIn our previous study, we revealed the ameliorative therapeutic effect of dexamethasone (Dex) for Lupus nephritis lesions in the MRL/MpJ-<i>Fas <sup>lpr/lpr</sup></i> (Lpr) mouse model. The female Lpr mice developed a greater number of mediastinal fat-associated lymphoid clusters (MFALCs) and inflammatory lung lesions compared to the male mice. However, the effect of Dex, an immunosuppressive drug, on both lung lesions and the development of MFALCs in Lpr mice has not been identified yet. Therefore, in this study, we compared the development of lung lesions and MFALCs in female Lpr mice that received either saline (saline group “SG”) or dexamethasone (dexamethasone group “DG”) in drinking water as a daily dose along with weekly intraperitoneal injections for 10 weeks. Compared to the SG group, the DG group showed a significant reduction in the levels of serum anti-dsDNA antibodies, the size of MFALCs, the degree of lung injury, the area of high endothelial venules (HEVs), and the number of proliferating and immune cells in both MFALCs and the lungs. A significant positive correlation was observed between the size of MFALCs and the cellular aggregation in the lungs of Lpr mice. Therefore, this study confirmed the ameliorative effect of Dex on the development of lung injury and MFALCs via their regressive effect on both immune cells’ proliferative activity and the development of HEVs. Furthermore, the reprogramming of MFALCs by targeting immune cells and HEVs may provide a therapeutic strategy for autoimmune-disease-associated lung injury.https://www.mdpi.com/1422-0067/23/8/4449autoimmune disease mouse modeldexamethasonehigh endothelial venuleslung injurylymphatic vesselsmediastinal fat-associated lymphoid cluster |
| spellingShingle | Yaser Hosny Ali Elewa Md Abdul Masum Sherif Kh. A. Mohamed Md Rashedul Islam Teppei Nakamura Osamu Ichii Yasuhiro Kon The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model International Journal of Molecular Sciences autoimmune disease mouse model dexamethasone high endothelial venules lung injury lymphatic vessels mediastinal fat-associated lymphoid cluster |
| title | The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model |
| title_full | The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model |
| title_fullStr | The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model |
| title_full_unstemmed | The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model |
| title_short | The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model |
| title_sort | ameliorative effect of dexamethasone on the development of autoimmune lung injury and mediastinal fat associated lymphoid clusters in an autoimmune disease mouse model |
| topic | autoimmune disease mouse model dexamethasone high endothelial venules lung injury lymphatic vessels mediastinal fat-associated lymphoid cluster |
| url | https://www.mdpi.com/1422-0067/23/8/4449 |
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