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Generation and Immune Regulation of CD4(+)CD25(−)Foxp3(+) T Cells in Chronic Obstructive Pulmonary Disease
The imbalance of CD4(+)Foxp3(+) T cell subsets is reportedly involved in abnormal inflammatory immune responses in patients with chronic obstructive pulmonary disease (COPD). However, the possible role of CD4(+)CD25(−)Foxp3(+) T cells in immune regulation in COPD remains to be investigated. In the c...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392103/ https://www.ncbi.nlm.nih.gov/pubmed/30842769 http://dx.doi.org/10.3389/fimmu.2019.00220 |
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author | Wu, Jiang-Hua Zhou, Mei Jin, Yang Meng, Zhao-Ji Xiong, Xian-Zhi Sun, Sheng-Wen Miao, Shuai-Ying Han, Hong-Li Tao, Xiao-Nan |
author_facet | Wu, Jiang-Hua Zhou, Mei Jin, Yang Meng, Zhao-Ji Xiong, Xian-Zhi Sun, Sheng-Wen Miao, Shuai-Ying Han, Hong-Li Tao, Xiao-Nan |
author_sort | Wu, Jiang-Hua |
collection | PubMed |
description | The imbalance of CD4(+)Foxp3(+) T cell subsets is reportedly involved in abnormal inflammatory immune responses in patients with chronic obstructive pulmonary disease (COPD). However, the possible role of CD4(+)CD25(−)Foxp3(+) T cells in immune regulation in COPD remains to be investigated. In the current study, distribution and phenotypic characteristics of CD4(+)CD25(−)Foxp3(+) T cells from peripheral blood were determined by flow cytometry; the origin, immune function and ultimate fate of CD4(+)CD25(−)Foxp3(+) T cells were further explored in vitro. It was observed that circulating CD4(+)CD25(−)Foxp3(+) T cells were significantly increased in stable COPD patients (SCOPD) and resembled central memory or effector memory T cells. Compared with peripheral CD4(+)CD25(+)Foxp3(+) T cells, peripheral CD4(+)CD25(−)Foxp3(+) T cells showed a lower expression of Foxp3, CTLA-4, HELIOS, and TIGIT, but a higher expression of CD127 and KI-67, suggesting that CD4(+)CD25(−)Foxp3(+) T cells lost the expression of Tregs-associated molecules following the reduction in CD25. Unexpectedly, our study found that transforming growth factor-β1 (TGFβ1) decreased CD25 expression and played a critical role in the generation of CD4(+)CD25(−)Foxp3(+) T cells from CD4(+)CD25(+)Foxp3(+) T cells. Phenotypic analysis further revealed that both inducible and peripheral CD4(+)CD25(−)Foxp3(+) T cells exhibited the features of activated conventional T cells. Importantly, memory CD4(+)CD25(−)Foxp3(+) T cells facilitated the proliferation and differentiation of naïve CD4(+) T cells into Th17 cells in the presence of IL-1β, IL-6, IL-23, and TGFβ1. Finally, a fraction of CD4(+)CD25(−)Foxp3(+) T cells, exhibiting instability and plasticity, were converted to Th17 cells when subjected to Th17 cell-polarizing condition. Taken together, we propose that TGFβ1 is responsible for the generation of CD4(+)CD25(−)Foxp3(+) T cells, and these cells functionally exert an auxiliary effect on Th17 cells generation and might perpetuate chronic inflammation in COPD. |
format | Online Article Text |
id | pubmed-6392103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63921032019-03-06 Generation and Immune Regulation of CD4(+)CD25(−)Foxp3(+) T Cells in Chronic Obstructive Pulmonary Disease Wu, Jiang-Hua Zhou, Mei Jin, Yang Meng, Zhao-Ji Xiong, Xian-Zhi Sun, Sheng-Wen Miao, Shuai-Ying Han, Hong-Li Tao, Xiao-Nan Front Immunol Immunology The imbalance of CD4(+)Foxp3(+) T cell subsets is reportedly involved in abnormal inflammatory immune responses in patients with chronic obstructive pulmonary disease (COPD). However, the possible role of CD4(+)CD25(−)Foxp3(+) T cells in immune regulation in COPD remains to be investigated. In the current study, distribution and phenotypic characteristics of CD4(+)CD25(−)Foxp3(+) T cells from peripheral blood were determined by flow cytometry; the origin, immune function and ultimate fate of CD4(+)CD25(−)Foxp3(+) T cells were further explored in vitro. It was observed that circulating CD4(+)CD25(−)Foxp3(+) T cells were significantly increased in stable COPD patients (SCOPD) and resembled central memory or effector memory T cells. Compared with peripheral CD4(+)CD25(+)Foxp3(+) T cells, peripheral CD4(+)CD25(−)Foxp3(+) T cells showed a lower expression of Foxp3, CTLA-4, HELIOS, and TIGIT, but a higher expression of CD127 and KI-67, suggesting that CD4(+)CD25(−)Foxp3(+) T cells lost the expression of Tregs-associated molecules following the reduction in CD25. Unexpectedly, our study found that transforming growth factor-β1 (TGFβ1) decreased CD25 expression and played a critical role in the generation of CD4(+)CD25(−)Foxp3(+) T cells from CD4(+)CD25(+)Foxp3(+) T cells. Phenotypic analysis further revealed that both inducible and peripheral CD4(+)CD25(−)Foxp3(+) T cells exhibited the features of activated conventional T cells. Importantly, memory CD4(+)CD25(−)Foxp3(+) T cells facilitated the proliferation and differentiation of naïve CD4(+) T cells into Th17 cells in the presence of IL-1β, IL-6, IL-23, and TGFβ1. Finally, a fraction of CD4(+)CD25(−)Foxp3(+) T cells, exhibiting instability and plasticity, were converted to Th17 cells when subjected to Th17 cell-polarizing condition. Taken together, we propose that TGFβ1 is responsible for the generation of CD4(+)CD25(−)Foxp3(+) T cells, and these cells functionally exert an auxiliary effect on Th17 cells generation and might perpetuate chronic inflammation in COPD. Frontiers Media S.A. 2019-02-20 /pmc/articles/PMC6392103/ /pubmed/30842769 http://dx.doi.org/10.3389/fimmu.2019.00220 Text en Copyright © 2019 Wu, Zhou, Jin, Meng, Xiong, Sun, Miao, Han and Tao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Wu, Jiang-Hua Zhou, Mei Jin, Yang Meng, Zhao-Ji Xiong, Xian-Zhi Sun, Sheng-Wen Miao, Shuai-Ying Han, Hong-Li Tao, Xiao-Nan Generation and Immune Regulation of CD4(+)CD25(−)Foxp3(+) T Cells in Chronic Obstructive Pulmonary Disease |
title | Generation and Immune Regulation of CD4(+)CD25(−)Foxp3(+) T Cells in Chronic Obstructive Pulmonary Disease |
title_full | Generation and Immune Regulation of CD4(+)CD25(−)Foxp3(+) T Cells in Chronic Obstructive Pulmonary Disease |
title_fullStr | Generation and Immune Regulation of CD4(+)CD25(−)Foxp3(+) T Cells in Chronic Obstructive Pulmonary Disease |
title_full_unstemmed | Generation and Immune Regulation of CD4(+)CD25(−)Foxp3(+) T Cells in Chronic Obstructive Pulmonary Disease |
title_short | Generation and Immune Regulation of CD4(+)CD25(−)Foxp3(+) T Cells in Chronic Obstructive Pulmonary Disease |
title_sort | generation and immune regulation of cd4(+)cd25(−)foxp3(+) t cells in chronic obstructive pulmonary disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392103/ https://www.ncbi.nlm.nih.gov/pubmed/30842769 http://dx.doi.org/10.3389/fimmu.2019.00220 |
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