| Residential College | false |
| Status | 即將出版Forthcoming |
| Pre-Ligand Assembly Domain-Derived Recombinant Proteins of TNFR2 Inhibits the Expansion of CD4+Foxp3+ Regulatory T Cells | |
WEN-WEI LI; CHUANGEN LI; YANG YANG; YIBO CHEN; Yexuan Zhang; Hong Cai; Chon Kit CHOU; Xin Chen; Yuanjia Hu*; ZHONGHAO CHEN; YANG GAO; YIRU WANG; XIN CHEN ; Chon-Kit Chou
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| 2025-01 | |
| Source Publication | Journal of Leukocyte Biology
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| Abstract | There is compelling evidence that tumor necrosis factor (TNF) receptor type II (TNFR2) mediates the stimulatory effect of TNF on the activation of CD4+Foxp3+ regulatory T cells (Tregs). Tregs with high TNFR2 expression are critical components of tumor microenvironment (TCM), where they promote tumor progression by impeding anti-tumor immune responses. Thus, selectively targeting TNFR2 has emerged as a promising strategy to inhibit Treg activity and enhance antitumor immune responses. The pre-ligand-binding assembly domain (PLAD) is a conserved extracellular domain that subtly differs among TNF receptor family members, facilitating the ligand-independent assembly of receptor monomers into a spatially optimal trimer that favors ligand binding. Previous studies demonstrated that recombinant PLAD proteins derived from TNFR1 was able to inhibit TNFR1-mediated cell death and alleviated inflammatory conditions in mouse models. However, the functional properties of TNFR2-derived PLAD remain largely unexplored. In this study, we developed recombinant PLAD proteins from human and mouse TNFR2, as well as TNFR1, and evaluated their ability to interfere with TNF binding and Treg activation. All four PLAD proteins dose-dependently inhibited TNF-stimulated NF-κB transcriptional activity in HEK293 reporter cells. Among them, human TNFR2-derived PLAD exhibited relatively enhanced inhibitory effects compared to the other three in HEK293 reporter cells overexpressing TNFR2 but lacking TNFR1, and potently blocked TNF binding to TNFR2 on Jurkat cell surfaces. Furthermore, human TNFR2-derived PLAD significantly reduced the TNF-induced proliferative expansion of CD4+Foxp3+ Tregs in both mouse lymphocyte and human PBMC cultures. Our findings suggest that human TNFR2-derived PLAD merits further investigation for the cancer immunotherapy. |
| Document Type | Journal article |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | XIN CHEN; Chon-Kit Chou |
| Affiliation | University of Macau State Key Laboratory of Quality Research in Chinese Medicine: University of Macau Institute of Chinese Medical Science |
| First Author Affilication | University of Macau |
| Corresponding Author Affilication | University of Macau |
| Recommended Citation GB/T 7714 | WEN-WEI LI,CHUANGEN LI,YANG YANG,et al. Pre-Ligand Assembly Domain-Derived Recombinant Proteins of TNFR2 Inhibits the Expansion of CD4+Foxp3+ Regulatory T Cells[J]. Journal of Leukocyte Biology, 2025. |
| APA | WEN-WEI LI., CHUANGEN LI., YANG YANG., YIBO CHEN; Yexuan Zhang; Hong Cai; Chon Kit CHOU; Xin Chen; Yuanjia Hu*., ZHONGHAO CHEN., YANG GAO., YIRU WANG., XIN CHEN., & Chon-Kit Chou (2025). Pre-Ligand Assembly Domain-Derived Recombinant Proteins of TNFR2 Inhibits the Expansion of CD4+Foxp3+ Regulatory T Cells. Journal of Leukocyte Biology. |
| MLA | WEN-WEI LI,et al."Pre-Ligand Assembly Domain-Derived Recombinant Proteins of TNFR2 Inhibits the Expansion of CD4+Foxp3+ Regulatory T Cells".Journal of Leukocyte Biology (2025). |
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