EGFR mimotope alleviates renal fibrosis by promoting EGFR/RPL6/PCBP2 ternary complex formation
- 1Department of Nephrology, Shanghai Fifth People’s Hospital, Fudan University, Heqing Road, Shanghai, China
Abstract
Epidermal growth factor receptor (EGFR) signalling plays a crucial role in renal fibrosis. We previously demonstrated that EGFR mimotope vaccination could alleviate renal fibrosis by restoring major histocompatibility complex class IB (MHC-IB) expression in renal tubular epithelial cells and promoting MHC-IB-enriched exosome release. Intriguingly, the mechanism by which the EGFR mimotope affects MHC-IB remains unknown. In this study, we demonstrated that administering purified EGFR mimotope-induced antibodies (EM-pAb) can effectively upregulate ribosomal protein ligand (RPL)-6, poly (rC) binding protein 2 (PCBP2), and MHC-IB in tubular epithelial cells. Mechanistically, the EM-pAb promoted EGFR/ribosomal protein ligand 6 (RPL6)/poly (rC) binding protein 2 (PCBP2) functional ternary complex formation, re-established the binding capability of PCBP2 to MHC-IB β-chain, and further regulated the NK cell population. RPL6 was confirmed as the key orchestrator of the ternary complex formation. Rpl6CKI mice further revealed the protective role of RPL6 in the animal model of renal fibrosis. RPL6 and kidney function showed a significant correlation in patients with chronic kidney disease. Overall, our findings uncover the signalling pathway by which EGFR modulates MHC-IB and validate the regulatory role of EM-pAb in this signalling pathway, indicating the therapeutic potential of RPL6 in chronic kidney disease.
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BibTeX
@article{wu2026egfr,
title = {{EGFR mimotope alleviates renal fibrosis by promoting EGFR/RPL6/PCBP2 ternary complex formation}},
author = {Qing Wu and Yu Chen and Di Zhao and Yuxuan Zhou and Zhenhao Yang and Xiaojing Zhong and Jianying Niu and Lin Yang},
journal = {NPJ Vaccines},
year = {2026},
month = jul,
doi = {10.1038/s41541-026-01513-w},
url = {https://doi.org/10.1038/s41541-026-01513-w},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - EGFR mimotope alleviates renal fibrosis by promoting EGFR/RPL6/PCBP2 ternary complex formation
AU - Qing Wu
AU - Yu Chen
AU - Di Zhao
AU - Yuxuan Zhou
AU - Zhenhao Yang
AU - Xiaojing Zhong
AU - Jianying Niu
AU - Lin Yang
PY - 2026
DA - 2026/07/04
JO - NPJ Vaccines
DO - 10.1038/s41541-026-01513-w
UR - https://doi.org/10.1038/s41541-026-01513-w
AB - Epidermal growth factor receptor (EGFR) signalling plays a crucial role in renal fibrosis. We previously demonstrated that EGFR mimotope vaccination could alleviate renal fibrosis by restoring major histocompatibility complex class IB (MHC-IB) expression in renal tubular epithelial cells and promoting MHC-IB-enriched exosome release. Intriguingly, the mechanism by which the EGFR mimotope affects MHC-IB remains unknown. In this study, we demonstrated that administering purified EGFR mimotope-induced antibodies (EM-pAb) can effectively upregulate ribosomal protein ligand (RPL)-6, poly (rC) binding protein 2 (PCBP2), and MHC-IB in tubular epithelial cells. Mechanistically, the EM-pAb promoted EGFR/ribosomal protein ligand 6 (RPL6)/poly (rC) binding protein 2 (PCBP2) functional ternary complex formation, re-established the binding capability of PCBP2 to MHC-IB β-chain, and further regulated the NK cell population. RPL6 was confirmed as the key orchestrator of the ternary complex formation. Rpl6CKI mice further revealed the protective role of RPL6 in the animal model of renal fibrosis. RPL6 and kidney function showed a significant correlation in patients with chronic kidney disease. Overall, our findings uncover the signalling pathway by which EGFR modulates MHC-IB and validate the regulatory role of EM-pAb in this signalling pathway, indicating the therapeutic potential of RPL6 in chronic kidney disease.
SN - 2059-0105
ER -