BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-β pathway in chronic obstructive pulmonary disease
Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by continuous flow limitation and the immune system including macrophages and regulatory T lymphocytes (Tregs) is involved in COPD pathogenesis. In our previous study, we investigated that TGF-β/BAMBI pathway was assoc...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-019-0988-z |
| _version_ | 1819173209007718400 |
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| author | Sheng-Wen Sun Long Chen Mei Zhou Jiang-Hua Wu Zhao-Ji Meng Hong-Li Han Shuai-Ying Miao Chen-Chen Zhu Xian-Zhi Xiong |
| author_facet | Sheng-Wen Sun Long Chen Mei Zhou Jiang-Hua Wu Zhao-Ji Meng Hong-Li Han Shuai-Ying Miao Chen-Chen Zhu Xian-Zhi Xiong |
| author_sort | Sheng-Wen Sun |
| collection | DOAJ |
| description | Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by continuous flow limitation and the immune system including macrophages and regulatory T lymphocytes (Tregs) is involved in COPD pathogenesis. In our previous study, we investigated that TGF-β/BAMBI pathway was associated with COPD by regulating the balance of Th17/Treg. However, the role of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a pseudoreceptor of TGF-β signalling pathway, in regulating the immune system of COPD patients has not been fully studied. Hence, we speculate that the pseudoreceptor BAMBI may play roles in the regulation of M2 macrophages to induce the differentiation of CD4+ naïve T cells into Tregs and influence the immune response in COPD. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy nonsmokers (n = 12), healthy smokers (n = 10) and COPD patients (n = 20). Naïve CD4+ T cells and monocytes-induced macrophages were used for coculture assays. The phenotypic characteristics of macrophages and Tregs were determined by flow cytometry. The expression levels of BAMBI and the TGF-β/Smad pathway members in M2 macrophages were measured by a Western blot analysis. The monocyte-derived macrophages were stimulated with cigarette smoke extract (CSE, concentration of 0.02%) to simulate the smoking process in humans. pCMV-BAMBI was transfected into monocyte-derived M2 macrophages for subsequent co-culture assays and signalling pathway analysis. Results Our results showed that M2 macrophages could induce the differentiation of Tregs through the TGF-β/Smad signalling pathway. In addition, monocyte-derived macrophages from COPD patients highly expressed BAMBI, and had a low capacity to induce Tregs differentiation. The expression of BAMBI and the forced expiratory volume in 1 second (FEV1%) were negatively correlated in COPD. Furthermore, overexpression of BAMBI promoted the conversion of M2 macrophages to M1 macrophages via the TGF-β/Smad pathway. Conclusions We demonstrated that BAMBI could promote the polarization process of M2 macrophages to M1 macrophages via the TGF-β/Smad signalling pathway and that overexpression of BAMBI could decrease the ability of M2 macrophages to induce Treg differentiation. These findings may provide a potential mechanism by which blocking BAMBI could improve immune function to regulate COPD inflammatory conditions. |
| first_indexed | 2024-12-22T20:19:26Z |
| format | Article |
| id | doaj.art-49a0954523704879a4a05e42bee804e6 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-22T20:19:26Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-49a0954523704879a4a05e42bee804e62022-12-21T18:13:53ZengBMCRespiratory Research1465-993X2019-02-0120111010.1186/s12931-019-0988-zBAMBI regulates macrophages inducing the differentiation of Treg through the TGF-β pathway in chronic obstructive pulmonary diseaseSheng-Wen Sun0Long Chen1Mei Zhou2Jiang-Hua Wu3Zhao-Ji Meng4Hong-Li Han5Shuai-Ying Miao6Chen-Chen Zhu7Xian-Zhi Xiong8Department of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Chronic obstructive pulmonary disease (COPD) is characterized by continuous flow limitation and the immune system including macrophages and regulatory T lymphocytes (Tregs) is involved in COPD pathogenesis. In our previous study, we investigated that TGF-β/BAMBI pathway was associated with COPD by regulating the balance of Th17/Treg. However, the role of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a pseudoreceptor of TGF-β signalling pathway, in regulating the immune system of COPD patients has not been fully studied. Hence, we speculate that the pseudoreceptor BAMBI may play roles in the regulation of M2 macrophages to induce the differentiation of CD4+ naïve T cells into Tregs and influence the immune response in COPD. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy nonsmokers (n = 12), healthy smokers (n = 10) and COPD patients (n = 20). Naïve CD4+ T cells and monocytes-induced macrophages were used for coculture assays. The phenotypic characteristics of macrophages and Tregs were determined by flow cytometry. The expression levels of BAMBI and the TGF-β/Smad pathway members in M2 macrophages were measured by a Western blot analysis. The monocyte-derived macrophages were stimulated with cigarette smoke extract (CSE, concentration of 0.02%) to simulate the smoking process in humans. pCMV-BAMBI was transfected into monocyte-derived M2 macrophages for subsequent co-culture assays and signalling pathway analysis. Results Our results showed that M2 macrophages could induce the differentiation of Tregs through the TGF-β/Smad signalling pathway. In addition, monocyte-derived macrophages from COPD patients highly expressed BAMBI, and had a low capacity to induce Tregs differentiation. The expression of BAMBI and the forced expiratory volume in 1 second (FEV1%) were negatively correlated in COPD. Furthermore, overexpression of BAMBI promoted the conversion of M2 macrophages to M1 macrophages via the TGF-β/Smad pathway. Conclusions We demonstrated that BAMBI could promote the polarization process of M2 macrophages to M1 macrophages via the TGF-β/Smad signalling pathway and that overexpression of BAMBI could decrease the ability of M2 macrophages to induce Treg differentiation. These findings may provide a potential mechanism by which blocking BAMBI could improve immune function to regulate COPD inflammatory conditions.http://link.springer.com/article/10.1186/s12931-019-0988-zCOPDM2 macrophagesRegulatory T lymphocytesTGF-β/Smad signalling pathwayBAMBI |
| spellingShingle | Sheng-Wen Sun Long Chen Mei Zhou Jiang-Hua Wu Zhao-Ji Meng Hong-Li Han Shuai-Ying Miao Chen-Chen Zhu Xian-Zhi Xiong BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-β pathway in chronic obstructive pulmonary disease Respiratory Research COPD M2 macrophages Regulatory T lymphocytes TGF-β/Smad signalling pathway BAMBI |
| title | BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-β pathway in chronic obstructive pulmonary disease |
| title_full | BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-β pathway in chronic obstructive pulmonary disease |
| title_fullStr | BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-β pathway in chronic obstructive pulmonary disease |
| title_full_unstemmed | BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-β pathway in chronic obstructive pulmonary disease |
| title_short | BAMBI regulates macrophages inducing the differentiation of Treg through the TGF-β pathway in chronic obstructive pulmonary disease |
| title_sort | bambi regulates macrophages inducing the differentiation of treg through the tgf β pathway in chronic obstructive pulmonary disease |
| topic | COPD M2 macrophages Regulatory T lymphocytes TGF-β/Smad signalling pathway BAMBI |
| url | http://link.springer.com/article/10.1186/s12931-019-0988-z |
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