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pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition

Programmed cell death-ligand 1 (PD-L1)/PD-1 axis is critical for maintenance of immune homeostasis by limiting overactivation of effector T-cell responses. The impairment of PD-L1/PD-1 signals play an important role in the pathogenesis of inflammatory diseases, making this pathway an ideal target fo...

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Autores principales: Sun, Ying, Hu, Linhan, Yang, Peng, Zhang, Min, Wang, Xinwei, Xiao, He, Qiao, Chunxia, Wang, Jing, Luo, Longlong, Feng, Jiannan, Zheng, Yuanqiang, Wang, Yi, Shi, Yanchun, Chen, Guojiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733706/
https://www.ncbi.nlm.nih.gov/pubmed/35003115
http://dx.doi.org/10.3389/fimmu.2021.794226
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author Sun, Ying
Hu, Linhan
Yang, Peng
Zhang, Min
Wang, Xinwei
Xiao, He
Qiao, Chunxia
Wang, Jing
Luo, Longlong
Feng, Jiannan
Zheng, Yuanqiang
Wang, Yi
Shi, Yanchun
Chen, Guojiang
author_facet Sun, Ying
Hu, Linhan
Yang, Peng
Zhang, Min
Wang, Xinwei
Xiao, He
Qiao, Chunxia
Wang, Jing
Luo, Longlong
Feng, Jiannan
Zheng, Yuanqiang
Wang, Yi
Shi, Yanchun
Chen, Guojiang
author_sort Sun, Ying
collection PubMed
description Programmed cell death-ligand 1 (PD-L1)/PD-1 axis is critical for maintenance of immune homeostasis by limiting overactivation of effector T-cell responses. The impairment of PD-L1/PD-1 signals play an important role in the pathogenesis of inflammatory diseases, making this pathway an ideal target for novel therapeutics to induce immune tolerance. Given weakly acidic environment as a putative hallmark of inflammation, in this study we designed a new cargo by linking the ectodomain of murine PD-L1 to the N terminus of pHLIPs, a low pH-responding and membrane-insertion peptide, and demonstrated its potent immune-suppressive activity. Specifically, PD-L1-pHLIP spanned the cellular membrane and perfectly recognized its ligand PD-1 in acidic buffer. Immobile PD-L1-pHLIP actively inhibited T-cell proliferation and IFN-γ production. Importantly, soluble PD-L1-pHLIP retained its function to dampen T-cell responses under acidic condition instead of neutral aqueous solution. Overall, these data suggest that PD-L1-pHLIP has potentials to be a novel therapeutic avenue for T-cell-mediated inflammatory diseases.
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spelling pubmed-87337062022-01-07 pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition Sun, Ying Hu, Linhan Yang, Peng Zhang, Min Wang, Xinwei Xiao, He Qiao, Chunxia Wang, Jing Luo, Longlong Feng, Jiannan Zheng, Yuanqiang Wang, Yi Shi, Yanchun Chen, Guojiang Front Immunol Immunology Programmed cell death-ligand 1 (PD-L1)/PD-1 axis is critical for maintenance of immune homeostasis by limiting overactivation of effector T-cell responses. The impairment of PD-L1/PD-1 signals play an important role in the pathogenesis of inflammatory diseases, making this pathway an ideal target for novel therapeutics to induce immune tolerance. Given weakly acidic environment as a putative hallmark of inflammation, in this study we designed a new cargo by linking the ectodomain of murine PD-L1 to the N terminus of pHLIPs, a low pH-responding and membrane-insertion peptide, and demonstrated its potent immune-suppressive activity. Specifically, PD-L1-pHLIP spanned the cellular membrane and perfectly recognized its ligand PD-1 in acidic buffer. Immobile PD-L1-pHLIP actively inhibited T-cell proliferation and IFN-γ production. Importantly, soluble PD-L1-pHLIP retained its function to dampen T-cell responses under acidic condition instead of neutral aqueous solution. Overall, these data suggest that PD-L1-pHLIP has potentials to be a novel therapeutic avenue for T-cell-mediated inflammatory diseases. Frontiers Media S.A. 2021-12-23 /pmc/articles/PMC8733706/ /pubmed/35003115 http://dx.doi.org/10.3389/fimmu.2021.794226 Text en Copyright © 2021 Sun, Hu, Yang, Zhang, Wang, Xiao, Qiao, Wang, Luo, Feng, Zheng, Wang, Shi and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Sun, Ying
Hu, Linhan
Yang, Peng
Zhang, Min
Wang, Xinwei
Xiao, He
Qiao, Chunxia
Wang, Jing
Luo, Longlong
Feng, Jiannan
Zheng, Yuanqiang
Wang, Yi
Shi, Yanchun
Chen, Guojiang
pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition
title pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition
title_full pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition
title_fullStr pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition
title_full_unstemmed pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition
title_short pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition
title_sort ph low insertion peptide-modified programmed cell death-ligand 1 potently suppresses t-cell activation under acidic condition
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733706/
https://www.ncbi.nlm.nih.gov/pubmed/35003115
http://dx.doi.org/10.3389/fimmu.2021.794226
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