Dissection of the trans-endocytosis and signal inhibition functions of CTLA-4 through the study of a disease-associated Y139C mutation.

doi:10.1038/s41423-025-01348-w

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Article

Dissection of the trans-endocytosis and signal inhibition functions of CTLA-4 through the study of a disease-associated Y139C mutation.

Cellular & molecular immunology - 1 Nov 2025

Zhao Zhishan, Wu Peng, Li Qingman, Sun Di, Wu Lize, Xu Yiping, Zhao Fan, Wu Dandan, Chen Ziwei, Yuan Pengkun, Zhu Kaixiang, Jin Xuexiao, Wang Pengfei, An Chenyi, Neculai Dante, Chen Wei, Lu Meiping, Lu Linrong

Abstract excerpt

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) plays a crucial role in maintaining peripheral immune tolerance, but its mechanisms of action are highly complicated. Here, through the generation of a gene knock-in (KI) mouse carrying a CTLA-4 Y139C human patient-derived pathogenic mutation, we phenocopied the lethal autoimmune diseases in Ctla4 KO mice due to the impairment of Treg functions. Interestingly,...

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Topics

CTLA-4 Antigen
Animals
Humans
Signal Transduction
Mice

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Endocytosis

Mutation

T-Lymphocytes, Regulatory

Mice, Knockout

Mice, Inbred C57BL

Cell Proliferation

Gene Knock-In Techniques

Autoimmune Diseases

Source

Open in PubMed Open full text

Identifiers

PMID: 41068487
DOI: 10.1038/s41423-025-01348-w
PMCID: PMC12575816

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