A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung Inflammation
T helper (Th) cells orchestrate allergic lung inflammation in asthma pathogenesis. Th9 is a novel Th cell subset that mainly produces IL-9, a potent proinflammatory cytokine in asthma. A 7-amino acid peptide (7P) of the hypervariable region 1 (HVR1) of hepatitis C virus has been identified as an imp...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2020-01-01
|
Series: | Journal of Immunology Research |
Online Access: | http://dx.doi.org/10.1155/2020/4184380 |
id |
doaj-4812689a698d4f37897e1a0616c8b95d |
---|---|
record_format |
Article |
spelling |
doaj-4812689a698d4f37897e1a0616c8b95d2020-11-25T02:40:35ZengHindawi LimitedJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/41843804184380A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung InflammationWanzhou Zhao0Conghao Tan1Xi Yu2Ruihe Yu3Qibing Mei4Yun Cheng5The Nanjing Han & Zaenker Cancer Institute (NHZCI), OG Pharmaceuticals, Jiangdongbei Road 88, Nanjing, 210036 Jiangsu Province, ChinaSchool of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013 Jiangsu Province, ChinaThe Nanjing Han & Zaenker Cancer Institute (NHZCI), OG Pharmaceuticals, Jiangdongbei Road 88, Nanjing, 210036 Jiangsu Province, ChinaThe Nanjing Han & Zaenker Cancer Institute (NHZCI), OG Pharmaceuticals, Jiangdongbei Road 88, Nanjing, 210036 Jiangsu Province, ChinaLuzhou New Drug Evaluation and Research Center, Luzhou, 646000 Sichuan Province, ChinaThe Nanjing Han & Zaenker Cancer Institute (NHZCI), OG Pharmaceuticals, Jiangdongbei Road 88, Nanjing, 210036 Jiangsu Province, ChinaT helper (Th) cells orchestrate allergic lung inflammation in asthma pathogenesis. Th9 is a novel Th cell subset that mainly produces IL-9, a potent proinflammatory cytokine in asthma. A 7-amino acid peptide (7P) of the hypervariable region 1 (HVR1) of hepatitis C virus has been identified as an important regulator in the type 2 cytokine (IL-4, IL-5, and IL-13) immune response. However, it is unknown whether 7P regulates Th9 cell differentiation during ovalbumin- (OVA-) induced allergic lung inflammation. To address this, we studied wild-type mice treated with 7P and a control peptide in an in vivo mouse model of OVA-induced allergic inflammation and an in vitro cell model of Th9 differentiation, using flow cytometry, cytokine assays, and quantitative PCR. The binding of 7P to CD81 on naïve CD4+ T cells during lung Th9 differentiation was determined using CD81 overexpression and siRNA knockdown analyses. Administration of 7P significantly reduced Th9 cell differentiation after OVA sensitization and exposure. 7P also inhibited Th9 cell differentiation from naïve and memory CD4+ T cells in vitro. Furthermore, 7P inhibited the differentiation of human Th9 cells with high CD81 expression from naïve CD4+ T cells by blocking CD81 signaling. CD81 siRNA significantly reduced Th9 cell differentiation from naïve CD4+ T cells in vitro. Interestingly, CD81 overexpression in human naïve CD4+ T cells also enhanced Th9 development in vitro. These data indicate that 7P may be a good candidate for reducing IL-9 production in asthma.http://dx.doi.org/10.1155/2020/4184380 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wanzhou Zhao Conghao Tan Xi Yu Ruihe Yu Qibing Mei Yun Cheng |
spellingShingle |
Wanzhou Zhao Conghao Tan Xi Yu Ruihe Yu Qibing Mei Yun Cheng A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung Inflammation Journal of Immunology Research |
author_facet |
Wanzhou Zhao Conghao Tan Xi Yu Ruihe Yu Qibing Mei Yun Cheng |
author_sort |
Wanzhou Zhao |
title |
A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung Inflammation |
title_short |
A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung Inflammation |
title_full |
A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung Inflammation |
title_fullStr |
A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung Inflammation |
title_full_unstemmed |
A 7-Amino Acid Peptide Mimic from Hepatitis C Virus Hypervariable Region 1 Inhibits Mouse Lung Th9 Cell Differentiation by Blocking CD81 Signaling during Allergic Lung Inflammation |
title_sort |
7-amino acid peptide mimic from hepatitis c virus hypervariable region 1 inhibits mouse lung th9 cell differentiation by blocking cd81 signaling during allergic lung inflammation |
publisher |
Hindawi Limited |
series |
Journal of Immunology Research |
issn |
2314-8861 2314-7156 |
publishDate |
2020-01-01 |
description |
T helper (Th) cells orchestrate allergic lung inflammation in asthma pathogenesis. Th9 is a novel Th cell subset that mainly produces IL-9, a potent proinflammatory cytokine in asthma. A 7-amino acid peptide (7P) of the hypervariable region 1 (HVR1) of hepatitis C virus has been identified as an important regulator in the type 2 cytokine (IL-4, IL-5, and IL-13) immune response. However, it is unknown whether 7P regulates Th9 cell differentiation during ovalbumin- (OVA-) induced allergic lung inflammation. To address this, we studied wild-type mice treated with 7P and a control peptide in an in vivo mouse model of OVA-induced allergic inflammation and an in vitro cell model of Th9 differentiation, using flow cytometry, cytokine assays, and quantitative PCR. The binding of 7P to CD81 on naïve CD4+ T cells during lung Th9 differentiation was determined using CD81 overexpression and siRNA knockdown analyses. Administration of 7P significantly reduced Th9 cell differentiation after OVA sensitization and exposure. 7P also inhibited Th9 cell differentiation from naïve and memory CD4+ T cells in vitro. Furthermore, 7P inhibited the differentiation of human Th9 cells with high CD81 expression from naïve CD4+ T cells by blocking CD81 signaling. CD81 siRNA significantly reduced Th9 cell differentiation from naïve CD4+ T cells in vitro. Interestingly, CD81 overexpression in human naïve CD4+ T cells also enhanced Th9 development in vitro. These data indicate that 7P may be a good candidate for reducing IL-9 production in asthma. |
url |
http://dx.doi.org/10.1155/2020/4184380 |
work_keys_str_mv |
AT wanzhouzhao a7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT conghaotan a7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT xiyu a7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT ruiheyu a7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT qibingmei a7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT yuncheng a7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT wanzhouzhao 7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT conghaotan 7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT xiyu 7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT ruiheyu 7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT qibingmei 7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation AT yuncheng 7aminoacidpeptidemimicfromhepatitiscvirushypervariableregion1inhibitsmouselungth9celldifferentiationbyblockingcd81signalingduringallergiclunginflammation |
_version_ |
1715417326009974784 |