Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization
Progranulin (PGRN), which plays an anti-inflammatory role in acute lung injury (ALI), is promising as a potential drug. Studies have shown that regulatory T cells (Tregs) and interleukin- (IL-) 10 can repress inflammation and alleviate tissue damage during ALI. In this study, we built a lipopolysacc...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/9704327 |
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| author | Yan-qing Chen Chuan-jiang Wang Ke Xie Ming Lei Yu-sen Chai Fang Xu Shi-hui Lin |
| author_facet | Yan-qing Chen Chuan-jiang Wang Ke Xie Ming Lei Yu-sen Chai Fang Xu Shi-hui Lin |
| author_sort | Yan-qing Chen |
| collection | DOAJ |
| description | Progranulin (PGRN), which plays an anti-inflammatory role in acute lung injury (ALI), is promising as a potential drug. Studies have shown that regulatory T cells (Tregs) and interleukin- (IL-) 10 can repress inflammation and alleviate tissue damage during ALI. In this study, we built a lipopolysaccharide- (LPS-) induced ALI mouse model to illustrate the effect of PGRN on regulation of Treg differentiation and modulation of IL-10 promoting macrophage polarization. We found that the proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells was higher after treatment with PGRN. The increased proportion of Tregs after PGRN intratracheal instillation was consistent with the decreased severity of lung injury, the reduction of proinflammatory cytokines, and the increase of anti-inflammatory cytokines. In vitro, the percentages of CD4+CD25+FOXP3+ Tregs from splenic naïve CD4+ T cells increased after PGRN treatment. In further research, it was found that PGRN can regulate the anti-inflammatory factor IL-10 and affect the polarization of M1/M2 macrophages by upregulating IL-10. These findings show that PGRN likely plays a protective role in ALI by promoting Treg differentiation and activating IL-10 immunomodulation. |
| format | Article |
| id | doaj-art-467b0d0567d54e02bf443502bb2649ca |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-467b0d0567d54e02bf443502bb2649ca2025-08-20T02:37:49ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/97043279704327Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage PolarizationYan-qing Chen0Chuan-jiang Wang1Ke Xie2Ming Lei3Yu-sen Chai4Fang Xu5Shi-hui Lin6Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaProgranulin (PGRN), which plays an anti-inflammatory role in acute lung injury (ALI), is promising as a potential drug. Studies have shown that regulatory T cells (Tregs) and interleukin- (IL-) 10 can repress inflammation and alleviate tissue damage during ALI. In this study, we built a lipopolysaccharide- (LPS-) induced ALI mouse model to illustrate the effect of PGRN on regulation of Treg differentiation and modulation of IL-10 promoting macrophage polarization. We found that the proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells was higher after treatment with PGRN. The increased proportion of Tregs after PGRN intratracheal instillation was consistent with the decreased severity of lung injury, the reduction of proinflammatory cytokines, and the increase of anti-inflammatory cytokines. In vitro, the percentages of CD4+CD25+FOXP3+ Tregs from splenic naïve CD4+ T cells increased after PGRN treatment. In further research, it was found that PGRN can regulate the anti-inflammatory factor IL-10 and affect the polarization of M1/M2 macrophages by upregulating IL-10. These findings show that PGRN likely plays a protective role in ALI by promoting Treg differentiation and activating IL-10 immunomodulation.http://dx.doi.org/10.1155/2020/9704327 |
| spellingShingle | Yan-qing Chen Chuan-jiang Wang Ke Xie Ming Lei Yu-sen Chai Fang Xu Shi-hui Lin Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization Mediators of Inflammation |
| title | Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization |
| title_full | Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization |
| title_fullStr | Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization |
| title_full_unstemmed | Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization |
| title_short | Progranulin Improves Acute Lung Injury through Regulating the Differentiation of Regulatory T Cells and Interleukin-10 Immunomodulation to Promote Macrophage Polarization |
| title_sort | progranulin improves acute lung injury through regulating the differentiation of regulatory t cells and interleukin 10 immunomodulation to promote macrophage polarization |
| url | http://dx.doi.org/10.1155/2020/9704327 |
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