DPP4 Regulates the Th17/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL/6J Mice

Background: Dipeptidyl peptidase-4 (DPP4) is a transmembrane glycoprotein, prevalent across a variety of tissues and cells and can be foundin a solubilised in peripheral blood. This paper aims at determining the role of sCD26/sDPP4 in Th17 cell polarization and airway epithelial cell to epithelial m...

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Main Authors: Linqiao Li, Feixiang Ling, Rou Li, Yan Jiang, Haiyan Long, Bo Xiao, Jingjie Wu, Zhiheng Long, Libing Ma
Format: Article
Language:English
Published: IMR Press 2023-12-01
Series:Frontiers in Bioscience-Landmark
Subjects:
Online Access:https://www.imrpress.com/journal/FBL/28/12/10.31083/j.fbl2812342
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author Linqiao Li
Feixiang Ling
Rou Li
Yan Jiang
Haiyan Long
Bo Xiao
Jingjie Wu
Zhiheng Long
Libing Ma
author_facet Linqiao Li
Feixiang Ling
Rou Li
Yan Jiang
Haiyan Long
Bo Xiao
Jingjie Wu
Zhiheng Long
Libing Ma
author_sort Linqiao Li
collection DOAJ
description Background: Dipeptidyl peptidase-4 (DPP4) is a transmembrane glycoprotein, prevalent across a variety of tissues and cells and can be foundin a solubilised in peripheral blood. This paper aims at determining the role of sCD26/sDPP4 in Th17 cell polarization and airway epithelial cell to epithelial mesenchymal transition (EMT) in asthma. Methods: Female C57BL/6J mice were treated with ovalbumin to constructed asthma mice. The CD4+ T cell, and bronchial epithelial cells (BECs) were purified from the spleens and bronchus of mice. The KRT8 expression in BECs were identified by immunofluorescence (IF). Th17 cells were differentiated from a CD4+ T cell. Flow cytometry was usewd to identify and calculate the Th17 and Treg cells. Mice woth asthma were treated by DPP4 overexpressing lentivirus or DPP4 inhibitor. Histopathological modifications were assessed by hematoxylin-eosin (HE), periodic acid Schiff (PAS), and Masson staining. The total number of leucocytes was detected using a hemocytometer. For detection, quantitative Real-time PCR (qRT-PCR), western blotting (WB), and IF were used to evaluate the expression of E-cadherin and alpha-smooth muscle actin (α-SMA). Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the DPP4, IL-4, IL-5, IL-13 and IL-17 levels. Results: The findings suggest that sCD26/sDPP4 promote CD4+ T cells differentiation into Th17 cells in a depending on the applied dose. sCD26/sDPP4 up-regulated the expression of α-SMA and down-regulated the expression of E-cadherin in TGF-β1-induced mouse BECs, which was reversed by DPP4 inhibitor. Co-culture induced a synergic effect between Th17 cells and sCD26/sDPP4 on the formation of airway EMT in BECs. Furthermore, DPP4 inhibitor prevented lung-bronchial inflammatory infiltration, mucus secretion, goblet cell hyperplasia and collagen deposition in asthma mice. Meanwhile, DPP4 inhibitor decreased the levels of DPP4, IL-4, IL-5, IL-13, IL-17 and increased the total number of leukocytes in bronchoalveolar lavage fluid of asthma mice. In addition, DPP4 inhibitor also inhibited airway EMT and Th17 cell polarization in asthma mice. Conclusions: The results in this paper show that up-regulation of DPP4 enabled airway inflammation and airway remodeling in asthmatic mice by modulating the Th17/IL-17 axis and accelerating the airway EMT, which isa therapeutic target in asthma.
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spelling doaj.art-f46ae80dad1847a09fb01a60555563d92024-01-05T10:10:07ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-12-01281234210.31083/j.fbl2812342S2768-6701(23)01019-5DPP4 Regulates the Th17/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL/6J MiceLinqiao Li0Feixiang Ling1Rou Li2Yan Jiang3Haiyan Long4Bo Xiao5Jingjie Wu6Zhiheng Long7Libing Ma8Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, ChinaBackground: Dipeptidyl peptidase-4 (DPP4) is a transmembrane glycoprotein, prevalent across a variety of tissues and cells and can be foundin a solubilised in peripheral blood. This paper aims at determining the role of sCD26/sDPP4 in Th17 cell polarization and airway epithelial cell to epithelial mesenchymal transition (EMT) in asthma. Methods: Female C57BL/6J mice were treated with ovalbumin to constructed asthma mice. The CD4+ T cell, and bronchial epithelial cells (BECs) were purified from the spleens and bronchus of mice. The KRT8 expression in BECs were identified by immunofluorescence (IF). Th17 cells were differentiated from a CD4+ T cell. Flow cytometry was usewd to identify and calculate the Th17 and Treg cells. Mice woth asthma were treated by DPP4 overexpressing lentivirus or DPP4 inhibitor. Histopathological modifications were assessed by hematoxylin-eosin (HE), periodic acid Schiff (PAS), and Masson staining. The total number of leucocytes was detected using a hemocytometer. For detection, quantitative Real-time PCR (qRT-PCR), western blotting (WB), and IF were used to evaluate the expression of E-cadherin and alpha-smooth muscle actin (α-SMA). Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the DPP4, IL-4, IL-5, IL-13 and IL-17 levels. Results: The findings suggest that sCD26/sDPP4 promote CD4+ T cells differentiation into Th17 cells in a depending on the applied dose. sCD26/sDPP4 up-regulated the expression of α-SMA and down-regulated the expression of E-cadherin in TGF-β1-induced mouse BECs, which was reversed by DPP4 inhibitor. Co-culture induced a synergic effect between Th17 cells and sCD26/sDPP4 on the formation of airway EMT in BECs. Furthermore, DPP4 inhibitor prevented lung-bronchial inflammatory infiltration, mucus secretion, goblet cell hyperplasia and collagen deposition in asthma mice. Meanwhile, DPP4 inhibitor decreased the levels of DPP4, IL-4, IL-5, IL-13, IL-17 and increased the total number of leukocytes in bronchoalveolar lavage fluid of asthma mice. In addition, DPP4 inhibitor also inhibited airway EMT and Th17 cell polarization in asthma mice. Conclusions: The results in this paper show that up-regulation of DPP4 enabled airway inflammation and airway remodeling in asthmatic mice by modulating the Th17/IL-17 axis and accelerating the airway EMT, which isa therapeutic target in asthma.https://www.imrpress.com/journal/FBL/28/12/10.31083/j.fbl2812342dpp4dpp4 inhibitorepithelial mesenchymal transitionasthma
spellingShingle Linqiao Li
Feixiang Ling
Rou Li
Yan Jiang
Haiyan Long
Bo Xiao
Jingjie Wu
Zhiheng Long
Libing Ma
DPP4 Regulates the Th17/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL/6J Mice
Frontiers in Bioscience-Landmark
dpp4
dpp4 inhibitor
epithelial mesenchymal transition
asthma
title DPP4 Regulates the Th17/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL/6J Mice
title_full DPP4 Regulates the Th17/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL/6J Mice
title_fullStr DPP4 Regulates the Th17/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL/6J Mice
title_full_unstemmed DPP4 Regulates the Th17/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL/6J Mice
title_short DPP4 Regulates the Th17/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL/6J Mice
title_sort dpp4 regulates the th17 il 17 axis and accelerates epithelial mesenchymal transition to promote ovalbumin induced asthma in female c57bl 6j mice
topic dpp4
dpp4 inhibitor
epithelial mesenchymal transition
asthma
url https://www.imrpress.com/journal/FBL/28/12/10.31083/j.fbl2812342
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