pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition.
|
| Abstract |
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.
|
|---|---|
| Authors | Ying Sun, Linhan Hu, Peng Yang, Min Zhang, Xinwei Wang, He Xiao, Chunxia Qiao, Jing Wang, Longlong Luo, Jiannan Feng, Yuanqiang Zheng, Yi Wang, Yanchun Shi, Guojiang Chen |
| Journal | Frontiers in immunology (Front Immunol) Vol. 12 Pg. 794226 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland |
| PMID | 35003115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2021 Sun, Hu, Yang, Zhang, Wang, Xiao, Qiao, Wang, Luo, Feng, Zheng, Wang, Shi and Chen. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!