Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Recent studies suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE. To investigate the mechanism of CTSS in SLE, CTSS-overexpressing transgenic (TG) mice were gener...

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Main Authors: Jinhee Lee, Soyoung Jang, Minjee Choi, Mincheol Kang, Su-Geun Lim, SI-Yong Kim, Soyeon Jang, Jiwon Ko, Eungyung Kim, Junkoo Yi, Yeonsik Choo, Myoung Ok Kim, Zae Young Ryoo
Format: Article
Language:English
Published: Nature Publishing Group 2021-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-94855-5
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spelling doaj-527c6365fe894cf79ff097e3b7400ebd2021-08-15T11:27:59ZengNature Publishing GroupScientific Reports2045-23222021-08-011111810.1038/s41598-021-94855-5Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic miceJinhee Lee0Soyoung Jang1Minjee Choi2Mincheol Kang3Su-Geun Lim4SI-Yong Kim5Soyeon Jang6Jiwon Ko7Eungyung Kim8Junkoo Yi9Yeonsik Choo10Myoung Ok Kim11Zae Young Ryoo12School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National UniversitySchool of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National UniversityCore Protein Resources Center, DGISTDepartment of Physiology and Cell Biology, School of Medicine, University of Nevada RenoSchool of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National UniversitySchool of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National UniversitySchool of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National UniversitySchool of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National UniversityDepartment of Animal Science and Biotechnology, Kyungpook National UniversityGyeongsangbukdo Livestock Research InstituteDepartment of Biology, Kyungpook National UniversityDepartment of Animal Science and Biotechnology, Kyungpook National UniversitySchool of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National UniversityAbstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Recent studies suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE. To investigate the mechanism of CTSS in SLE, CTSS-overexpressing transgenic (TG) mice were generated, and induced lupus-like symptoms. Eight months later, the TG mice spontaneously developed typical SLE symptoms regardless of the inducement. Furthermore, we observed increased toll-like receptor 7 (TLR7) expression with increased monocyte and neutrophil populations in the TG mice. In conclusion, overexpression of CTSS in mice influences TLR7 expression, autoantibodies and IFN-α, which leads to an autoimmune reaction and exacerbates lupus-like symptoms.https://doi.org/10.1038/s41598-021-94855-5
collection DOAJ
language English
format Article
sources DOAJ
author Jinhee Lee
Soyoung Jang
Minjee Choi
Mincheol Kang
Su-Geun Lim
SI-Yong Kim
Soyeon Jang
Jiwon Ko
Eungyung Kim
Junkoo Yi
Yeonsik Choo
Myoung Ok Kim
Zae Young Ryoo
spellingShingle Jinhee Lee
Soyoung Jang
Minjee Choi
Mincheol Kang
Su-Geun Lim
SI-Yong Kim
Soyeon Jang
Jiwon Ko
Eungyung Kim
Junkoo Yi
Yeonsik Choo
Myoung Ok Kim
Zae Young Ryoo
Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice
Scientific Reports
author_facet Jinhee Lee
Soyoung Jang
Minjee Choi
Mincheol Kang
Su-Geun Lim
SI-Yong Kim
Soyeon Jang
Jiwon Ko
Eungyung Kim
Junkoo Yi
Yeonsik Choo
Myoung Ok Kim
Zae Young Ryoo
author_sort Jinhee Lee
title Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice
title_short Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice
title_full Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice
title_fullStr Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice
title_full_unstemmed Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice
title_sort overexpression of cathepsin s exacerbates lupus pathogenesis through upregulation tlr7 and ifn-α in transgenic mice
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-08-01
description Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Recent studies suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE. To investigate the mechanism of CTSS in SLE, CTSS-overexpressing transgenic (TG) mice were generated, and induced lupus-like symptoms. Eight months later, the TG mice spontaneously developed typical SLE symptoms regardless of the inducement. Furthermore, we observed increased toll-like receptor 7 (TLR7) expression with increased monocyte and neutrophil populations in the TG mice. In conclusion, overexpression of CTSS in mice influences TLR7 expression, autoantibodies and IFN-α, which leads to an autoimmune reaction and exacerbates lupus-like symptoms.
url https://doi.org/10.1038/s41598-021-94855-5
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