Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune Emphysema

Our previous study suggested that hypomethylation of perforin promoter of CD4 + T cells might be involved in the pathogenesis of autoimmune emphysema of rats. Whether transfer of this kind of cells hypomethylated in vitro into naive immunocompetent rats also results in emphysema is unknown yet. To t...

Full description

Bibliographic Details
Main Authors: Jia-jia Liu, Lin Liu, Hong-hong Mu, Jia-yi Li, Lin Xu, Yao-yao Wu, Ben-xue Li, Ye Zhang, Xiang-yan Zhang, Xian-wei Ye, Cheng Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:COPD
Subjects:
Online Access:http://dx.doi.org/10.1080/15412555.2022.2072720
_version_ 1797403974345687040
author Jia-jia Liu
Lin Liu
Hong-hong Mu
Jia-yi Li
Lin Xu
Yao-yao Wu
Ben-xue Li
Ye Zhang
Xiang-yan Zhang
Xian-wei Ye
Cheng Zhang
author_facet Jia-jia Liu
Lin Liu
Hong-hong Mu
Jia-yi Li
Lin Xu
Yao-yao Wu
Ben-xue Li
Ye Zhang
Xiang-yan Zhang
Xian-wei Ye
Cheng Zhang
author_sort Jia-jia Liu
collection DOAJ
description Our previous study suggested that hypomethylation of perforin promoter of CD4 + T cells might be involved in the pathogenesis of autoimmune emphysema of rats. Whether transfer of this kind of cells hypomethylated in vitro into naive immunocompetent rats also results in emphysema is unknown yet. To test the hypothesis above, thirty Sprague Dawley (SD) rats were randomly divided into three groups: a model group (n = 10), a normal control group (n = 10) and a sham operation group (n = 10). In the model group, spleen-derived CD4 + T cells of normal rats were treated with 5-azacytidine (5-Aza), complete Freund’s adjuvant and Phosphate Buffered Saline (PBS), then transferred into naive immunocompetent rats. The normal control group was injected with CD4 + T lymphocytes from spleens of normal rats and the same amount of adjuvant and PBS as above. In sham operation group, normal rats were injected intraperitoneally with complete Freund’s adjuvant and PBS. Histopathological evaluations (mean linear Intercept (MLI) and mean alveolar numbers (MAN)), anti-endothelial cell antibodies (AECA) in serum and bronchoalveolar lavage fluid (BALF), lung vascular endothelial growth factor (VEGF)), the apoptotic index (AI) of alveolar septal cells and the methylation levels of perforin promoter of CD4 + T cells were investigated. The levels of the methylation above and MAN were lower in the model group than in the control and the sham operation group, while the AECA in serum and BALF, VEGF, MLI and the AI were greater (all p < 0.05). The methylation levels of perforin promoter were positively correlated with the MAN (r = 0.747, p < 0.05) and negatively correlated with AI, AECA, MLI, and VEGF (r was −0.789, −0.746, −0.743, −0.660, respectively, all p < 0.05). This study suggests that transfer of invitro CD4 + T cells with hypomethylation of perforin promoter into rats causes autoimmune emphysema, possibly by increasing expression of VEGF and promoting alveolar septal cell apoptosis.
first_indexed 2024-03-09T02:47:29Z
format Article
id doaj.art-7ff76013fde9443c99807eab9c570f73
institution Directory Open Access Journal
issn 1541-2555
1541-2563
language English
last_indexed 2024-03-09T02:47:29Z
publishDate 2022-12-01
publisher Taylor & Francis Group
record_format Article
series COPD
spelling doaj.art-7ff76013fde9443c99807eab9c570f732023-12-05T16:09:50ZengTaylor & Francis GroupCOPD1541-25551541-25632022-12-0119125526110.1080/15412555.2022.20727202072720Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune EmphysemaJia-jia Liu0Lin Liu1Hong-hong Mu2Jia-yi Li3Lin Xu4Yao-yao Wu5Ben-xue Li6Ye Zhang7Xiang-yan Zhang8Xian-wei Ye9Cheng Zhang10Department of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalDepartment of Respiratory Medicine, Guizhou Provincial People’s HospitalOur previous study suggested that hypomethylation of perforin promoter of CD4 + T cells might be involved in the pathogenesis of autoimmune emphysema of rats. Whether transfer of this kind of cells hypomethylated in vitro into naive immunocompetent rats also results in emphysema is unknown yet. To test the hypothesis above, thirty Sprague Dawley (SD) rats were randomly divided into three groups: a model group (n = 10), a normal control group (n = 10) and a sham operation group (n = 10). In the model group, spleen-derived CD4 + T cells of normal rats were treated with 5-azacytidine (5-Aza), complete Freund’s adjuvant and Phosphate Buffered Saline (PBS), then transferred into naive immunocompetent rats. The normal control group was injected with CD4 + T lymphocytes from spleens of normal rats and the same amount of adjuvant and PBS as above. In sham operation group, normal rats were injected intraperitoneally with complete Freund’s adjuvant and PBS. Histopathological evaluations (mean linear Intercept (MLI) and mean alveolar numbers (MAN)), anti-endothelial cell antibodies (AECA) in serum and bronchoalveolar lavage fluid (BALF), lung vascular endothelial growth factor (VEGF)), the apoptotic index (AI) of alveolar septal cells and the methylation levels of perforin promoter of CD4 + T cells were investigated. The levels of the methylation above and MAN were lower in the model group than in the control and the sham operation group, while the AECA in serum and BALF, VEGF, MLI and the AI were greater (all p < 0.05). The methylation levels of perforin promoter were positively correlated with the MAN (r = 0.747, p < 0.05) and negatively correlated with AI, AECA, MLI, and VEGF (r was −0.789, −0.746, −0.743, −0.660, respectively, all p < 0.05). This study suggests that transfer of invitro CD4 + T cells with hypomethylation of perforin promoter into rats causes autoimmune emphysema, possibly by increasing expression of VEGF and promoting alveolar septal cell apoptosis.http://dx.doi.org/10.1080/15412555.2022.2072720dna methylation invitro cd4 + t cellsperforin promoteralveolar septal cell apoptosisautoimmune emphysema
spellingShingle Jia-jia Liu
Lin Liu
Hong-hong Mu
Jia-yi Li
Lin Xu
Yao-yao Wu
Ben-xue Li
Ye Zhang
Xiang-yan Zhang
Xian-wei Ye
Cheng Zhang
Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune Emphysema
COPD
dna methylation invitro cd4 + t cells
perforin promoter
alveolar septal cell apoptosis
autoimmune emphysema
title Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune Emphysema
title_full Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune Emphysema
title_fullStr Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune Emphysema
title_full_unstemmed Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune Emphysema
title_short Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats’ Abdomens Causes Autoimmune Emphysema
title_sort transfer of invitro cd4 t cells with hypomethylation of perforin promoter into rats abdomens causes autoimmune emphysema
topic dna methylation invitro cd4 + t cells
perforin promoter
alveolar septal cell apoptosis
autoimmune emphysema
url http://dx.doi.org/10.1080/15412555.2022.2072720
work_keys_str_mv AT jiajialiu transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT linliu transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT honghongmu transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT jiayili transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT linxu transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT yaoyaowu transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT benxueli transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT yezhang transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT xiangyanzhang transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT xianweiye transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema
AT chengzhang transferofinvitrocd4tcellswithhypomethylationofperforinpromoterintoratsabdomenscausesautoimmuneemphysema