MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosis

The high prevalence of chronic kidney disease (CKD) is a significant public health burden worldwide. Renal fibrosis is an inevitable pathological process in almost all CKD cases. To date, the available treatments to prevent or delay renal fibrosis progression are limited. Epidermal growth factor rec...

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Main Authors: Jin Guo, Xuanqi Liu, Haoming Song, Yong Gu, Jianying Niu, Lin Yang
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Extracellular Vesicle
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Online Access:http://www.sciencedirect.com/science/article/pii/S2773041723000033
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author Jin Guo
Xuanqi Liu
Haoming Song
Yong Gu
Jianying Niu
Lin Yang
author_facet Jin Guo
Xuanqi Liu
Haoming Song
Yong Gu
Jianying Niu
Lin Yang
author_sort Jin Guo
collection DOAJ
description The high prevalence of chronic kidney disease (CKD) is a significant public health burden worldwide. Renal fibrosis is an inevitable pathological process in almost all CKD cases. To date, the available treatments to prevent or delay renal fibrosis progression are limited. Epidermal growth factor receptor (EGFR) mimotope has been demonstrated to alleviate renal fibrosis in the unilateral ureteric obstruction (UUO) model as a type of vaccine. Further observations suggested that the EGFR mimotope can inhibit the activation of macrophages, which play a vital role in renal fibrosis. In the current study, we explored the link triggered by the EGFR mimotopes between tubular epithelial cells (TECs) and macrophages. A series of experiments indicated that EGFR mimotope immunization can inhibit the activation of THP-1 macrophages by TEC-derived exosomes. Injection of these exosomes ameliorated renal fibrosis in the UUO model. Mechanism analysis suggested that the major histocompatibility complex-1B (MHC-1B) was the key molecule in the TECs exosomes induced by EGFR mimotope immunization and is regulated by ribosomal protein L6 (RPL-6). This study revealed a new specific working path of the EGFR mimotope and suggests that the application of the EGFR mimotope can be extended to other immune-related disorders.
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publishDate 2023-12-01
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spelling doaj-art-d29ca3f76dc94c4e84e1d73a0b7e6dc02024-11-23T06:34:52ZengElsevierExtracellular Vesicle2773-04172023-12-012100024MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosisJin Guo0Xuanqi Liu1Haoming Song2Yong Gu3Jianying Niu4Lin Yang5Department of Cardiorespiratory Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, No. 2209, Guangxing Road, Shanghai, ChinaDepartment of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, No. 321, Zhongshan Road, Nanjing, ChinaDepartment of Cardiology, Tongji Hospital, Tongji University School of Medicine, No. 389, Xincun Road, Shanghai, ChinaDepartment of Nephrology, Shanghai Fifth People’s Hospital, Fudan University, No. 801, Heqing Road, Shanghai, ChinaDepartment of Nephrology, Shanghai Fifth People’s Hospital, Fudan University, No. 801, Heqing Road, Shanghai, China; Corresponding author at: Department of Nephrology, Shanghai Fifth People’s Hospital, Fudan University, No. 801, Heqing Road, Shanghai 200240, China.Department of Nephrology, Shanghai Fifth People’s Hospital, Fudan University, No. 801, Heqing Road, Shanghai, China; Corresponding author at: Department of Nephrology, Shanghai Fifth People’s Hospital, Fudan University, No. 801, Heqing Road, Shanghai 200240, China.The high prevalence of chronic kidney disease (CKD) is a significant public health burden worldwide. Renal fibrosis is an inevitable pathological process in almost all CKD cases. To date, the available treatments to prevent or delay renal fibrosis progression are limited. Epidermal growth factor receptor (EGFR) mimotope has been demonstrated to alleviate renal fibrosis in the unilateral ureteric obstruction (UUO) model as a type of vaccine. Further observations suggested that the EGFR mimotope can inhibit the activation of macrophages, which play a vital role in renal fibrosis. In the current study, we explored the link triggered by the EGFR mimotopes between tubular epithelial cells (TECs) and macrophages. A series of experiments indicated that EGFR mimotope immunization can inhibit the activation of THP-1 macrophages by TEC-derived exosomes. Injection of these exosomes ameliorated renal fibrosis in the UUO model. Mechanism analysis suggested that the major histocompatibility complex-1B (MHC-1B) was the key molecule in the TECs exosomes induced by EGFR mimotope immunization and is regulated by ribosomal protein L6 (RPL-6). This study revealed a new specific working path of the EGFR mimotope and suggests that the application of the EGFR mimotope can be extended to other immune-related disorders.http://www.sciencedirect.com/science/article/pii/S2773041723000033Renal fibrosisMimotopeExosomeRibosomal protein L6Major histocompatibility complex-1B
spellingShingle Jin Guo
Xuanqi Liu
Haoming Song
Yong Gu
Jianying Niu
Lin Yang
MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosis
Extracellular Vesicle
Renal fibrosis
Mimotope
Exosome
Ribosomal protein L6
Major histocompatibility complex-1B
title MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosis
title_full MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosis
title_fullStr MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosis
title_full_unstemmed MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosis
title_short MHC-1B carried exosomes derived from tubular epithelial cell induced by the EGFR mimotope inhibit macrophage activation in renal fibrosis
title_sort mhc 1b carried exosomes derived from tubular epithelial cell induced by the egfr mimotope inhibit macrophage activation in renal fibrosis
topic Renal fibrosis
Mimotope
Exosome
Ribosomal protein L6
Major histocompatibility complex-1B
url http://www.sciencedirect.com/science/article/pii/S2773041723000033
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