Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease.
CD8+ T cells (Cytotoxic T cells, Tc) are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD). However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg) subsets, especia...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4726532?pdf=render |
| _version_ | 1819069929642524672 |
|---|---|
| author | Gang Chen Mei Zhou Long Chen Zhao-Ji Meng Xian-Zhi Xiong Hong-Ju Liu Jian-Bao Xin Jian-Chu Zhang |
| author_facet | Gang Chen Mei Zhou Long Chen Zhao-Ji Meng Xian-Zhi Xiong Hong-Ju Liu Jian-Bao Xin Jian-Chu Zhang |
| author_sort | Gang Chen |
| collection | DOAJ |
| description | CD8+ T cells (Cytotoxic T cells, Tc) are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD). However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg) subsets, especially by modulating muscarinic acetylcholine receptors (MRs), has yet to be well elucidated.Circulating CD8+ Tc/Tregs in healthy nonsmokers (n = 15), healthy smokers (n = 15) and COPD patients (n = 18) were evaluated by flow cytometry after incubating with anti-CD3, anti-CD8, anti-CD25, anti-Foxp3 antibodies. Peripheral blood T cells (PBT cells) from healthy nonsmokers were cultured in the presence of cigarette smoke extract (CSE) alone or combined with MRs agonist/antagonist for 5 days. Proliferation and apoptosis were evaluated by flow cytometry using Ki-67/Annexin-V antibodies to measure the effects of CSE on the survival of CD8+ Tc/Tregs.While COPD patients have elevated circulating percentage of CD8+ T cells, healthy smokers have higher frequency of CD8+ Tregs. Elevated percentages of CD8+ T cells correlated inversely with declined FEV1 in COPD. CSE promoted the proliferation and inhibited the apoptosis of CD8+ T cells, while facilitated both the proliferation and apoptosis of CD8+ Tregs. Notably, the effects of CSE on CD8+ Tc/Tregs can be mostly simulated or attenuated by muscarine and atropine, the MR agonist and antagonist, respectively. However, neither muscarine nor atropine influenced the apoptosis of CD8+ Tregs.The results imply that cigarette smoking likely facilitates a proinflammatory state in smokers, which is partially mediated by MR dysfunction. The MR antagonist may be a beneficial drug candidate for cigarette smoke-induced chronic airway inflammation. |
| first_indexed | 2024-12-21T16:57:51Z |
| format | Article |
| id | doaj.art-0ca48d91424b447ea68416ad69601d5b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T16:57:51Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0ca48d91424b447ea68416ad69601d5b2022-12-21T18:56:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014723210.1371/journal.pone.0147232Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease.Gang ChenMei ZhouLong ChenZhao-Ji MengXian-Zhi XiongHong-Ju LiuJian-Bao XinJian-Chu ZhangCD8+ T cells (Cytotoxic T cells, Tc) are known to play a critical role in the pathogenesis of smoking related airway inflammation including chronic obstructive pulmonary disease (COPD). However, how cigarette smoke directly impacts systematic CD8+ T cell and regulatory T cell (Treg) subsets, especially by modulating muscarinic acetylcholine receptors (MRs), has yet to be well elucidated.Circulating CD8+ Tc/Tregs in healthy nonsmokers (n = 15), healthy smokers (n = 15) and COPD patients (n = 18) were evaluated by flow cytometry after incubating with anti-CD3, anti-CD8, anti-CD25, anti-Foxp3 antibodies. Peripheral blood T cells (PBT cells) from healthy nonsmokers were cultured in the presence of cigarette smoke extract (CSE) alone or combined with MRs agonist/antagonist for 5 days. Proliferation and apoptosis were evaluated by flow cytometry using Ki-67/Annexin-V antibodies to measure the effects of CSE on the survival of CD8+ Tc/Tregs.While COPD patients have elevated circulating percentage of CD8+ T cells, healthy smokers have higher frequency of CD8+ Tregs. Elevated percentages of CD8+ T cells correlated inversely with declined FEV1 in COPD. CSE promoted the proliferation and inhibited the apoptosis of CD8+ T cells, while facilitated both the proliferation and apoptosis of CD8+ Tregs. Notably, the effects of CSE on CD8+ Tc/Tregs can be mostly simulated or attenuated by muscarine and atropine, the MR agonist and antagonist, respectively. However, neither muscarine nor atropine influenced the apoptosis of CD8+ Tregs.The results imply that cigarette smoking likely facilitates a proinflammatory state in smokers, which is partially mediated by MR dysfunction. The MR antagonist may be a beneficial drug candidate for cigarette smoke-induced chronic airway inflammation.http://europepmc.org/articles/PMC4726532?pdf=render |
| spellingShingle | Gang Chen Mei Zhou Long Chen Zhao-Ji Meng Xian-Zhi Xiong Hong-Ju Liu Jian-Bao Xin Jian-Chu Zhang Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease. PLoS ONE |
| title | Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease. |
| title_full | Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease. |
| title_fullStr | Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease. |
| title_full_unstemmed | Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease. |
| title_short | Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease. |
| title_sort | cigarette smoke disturbs the survival of cd8 tc tregs partially through muscarinic receptors dependent mechanisms in chronic obstructive pulmonary disease |
| url | http://europepmc.org/articles/PMC4726532?pdf=render |
| work_keys_str_mv | AT gangchen cigarettesmokedisturbsthesurvivalofcd8tctregspartiallythroughmuscarinicreceptorsdependentmechanismsinchronicobstructivepulmonarydisease AT meizhou cigarettesmokedisturbsthesurvivalofcd8tctregspartiallythroughmuscarinicreceptorsdependentmechanismsinchronicobstructivepulmonarydisease AT longchen cigarettesmokedisturbsthesurvivalofcd8tctregspartiallythroughmuscarinicreceptorsdependentmechanismsinchronicobstructivepulmonarydisease AT zhaojimeng cigarettesmokedisturbsthesurvivalofcd8tctregspartiallythroughmuscarinicreceptorsdependentmechanismsinchronicobstructivepulmonarydisease AT xianzhixiong cigarettesmokedisturbsthesurvivalofcd8tctregspartiallythroughmuscarinicreceptorsdependentmechanismsinchronicobstructivepulmonarydisease AT hongjuliu cigarettesmokedisturbsthesurvivalofcd8tctregspartiallythroughmuscarinicreceptorsdependentmechanismsinchronicobstructivepulmonarydisease AT jianbaoxin cigarettesmokedisturbsthesurvivalofcd8tctregspartiallythroughmuscarinicreceptorsdependentmechanismsinchronicobstructivepulmonarydisease AT jianchuzhang cigarettesmokedisturbsthesurvivalofcd8tctregspartiallythroughmuscarinicreceptorsdependentmechanismsinchronicobstructivepulmonarydisease |