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Reduced frequencies of Foxp3(+)GARP(+) regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype
BACKGROUND: Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of ch...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250745/ https://www.ncbi.nlm.nih.gov/pubmed/35780120 http://dx.doi.org/10.1186/s12931-022-02099-2 |
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author | Hou, Jia Wang, Xia Su, Chunxia Ma, Weirong Zheng, Xiwei Ge, Xiahui Duan, Xiangguo |
author_facet | Hou, Jia Wang, Xia Su, Chunxia Ma, Weirong Zheng, Xiwei Ge, Xiahui Duan, Xiangguo |
author_sort | Hou, Jia |
collection | PubMed |
description | BACKGROUND: Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism. OBJECTIVE: To investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD. METHODS: GARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed. RESULTS: Patients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3(+)GARP(+) Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3(+)GARP(−) Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood. CONCLUSION: Decreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02099-2. |
format | Online Article Text |
id | pubmed-9250745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-92507452022-07-04 Reduced frequencies of Foxp3(+)GARP(+) regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype Hou, Jia Wang, Xia Su, Chunxia Ma, Weirong Zheng, Xiwei Ge, Xiahui Duan, Xiangguo Respir Res Research BACKGROUND: Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism. OBJECTIVE: To investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD. METHODS: GARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed. RESULTS: Patients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3(+)GARP(+) Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3(+)GARP(−) Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood. CONCLUSION: Decreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02099-2. BioMed Central 2022-07-02 2022 /pmc/articles/PMC9250745/ /pubmed/35780120 http://dx.doi.org/10.1186/s12931-022-02099-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Hou, Jia Wang, Xia Su, Chunxia Ma, Weirong Zheng, Xiwei Ge, Xiahui Duan, Xiangguo Reduced frequencies of Foxp3(+)GARP(+) regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype |
title | Reduced frequencies of Foxp3(+)GARP(+) regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype |
title_full | Reduced frequencies of Foxp3(+)GARP(+) regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype |
title_fullStr | Reduced frequencies of Foxp3(+)GARP(+) regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype |
title_full_unstemmed | Reduced frequencies of Foxp3(+)GARP(+) regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype |
title_short | Reduced frequencies of Foxp3(+)GARP(+) regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype |
title_sort | reduced frequencies of foxp3(+)garp(+) regulatory t cells in copd patients are associated with multi-organ loss of tissue phenotype |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250745/ https://www.ncbi.nlm.nih.gov/pubmed/35780120 http://dx.doi.org/10.1186/s12931-022-02099-2 |
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