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Article: PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells
Title | PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells |
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Authors | |
Issue Date | 10-Nov-2023 |
Publisher | Life Science Alliance |
Citation | Life Science Alliance, 2023, v. 7, n. 2 How to Cite? |
Abstract | Programmed death ligand 1 (PD-L1) serves as a pivotal immune checkpoint in both the innate and adaptive immune systems. PD-L1 is expressed in macrophages in response to IFNγ. We examined whether PD-L1 might regulate macrophage development. We established PD-L1 KO (CD274-/-) human pluripotent stem cells and differentiated them into macrophages and observed a 60% reduction in CD11B+CD45+ macrophages in CD274-/-; this was orthogonally verified, with the PD-L1 inhibitor BMS-1166 reducing macrophages to the same fold. Single-cell RNA sequencing further confirmed the down-regulation of the macrophage-defining transcription factors SPI1 and MAFB. Furthermore, CD274-/- macrophages reduced the level of inflammatory signals such as NF-κB and TNF, and chemokine secretion of the CXCL and CCL families. Anti-inflammatory TGF-β was up-regulated. Finally, we identified that CD274-/- macrophages significantly down-regulated interferon-stimulated genes despite the presence of IFNγ in the differentiation media. These data suggest that PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells. |
Persistent Identifier | http://hdl.handle.net/10722/339069 |
ISSN | 2021 Impact Factor: 5.781 2020 SCImago Journal Rankings: 2.570 |
DC Field | Value | Language |
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dc.contributor.author | Cao, H | - |
dc.contributor.author | Xiang, Y | - |
dc.contributor.author | Zhang, S | - |
dc.contributor.author | Chao, Y | - |
dc.contributor.author | Guo, J | - |
dc.contributor.author | Aurich, T | - |
dc.contributor.author | Ho, JW | - |
dc.contributor.author | Huang, Y | - |
dc.contributor.author | Liu, P | - |
dc.contributor.author | Sugimura, R | - |
dc.date.accessioned | 2024-03-11T10:33:38Z | - |
dc.date.available | 2024-03-11T10:33:38Z | - |
dc.date.issued | 2023-11-10 | - |
dc.identifier.citation | Life Science Alliance, 2023, v. 7, n. 2 | - |
dc.identifier.issn | 2575-1077 | - |
dc.identifier.uri | http://hdl.handle.net/10722/339069 | - |
dc.description.abstract | <p>Programmed death ligand 1 (PD-L1) serves as a pivotal immune checkpoint in both the innate and adaptive immune systems. PD-L1 is expressed in macrophages in response to IFNγ. We examined whether PD-L1 might regulate macrophage development. We established PD-L1 KO (<em>CD274</em><sup><em>-/-</em></sup>) human pluripotent stem cells and differentiated them into macrophages and observed a 60% reduction in CD11B<sup>+</sup>CD45<sup>+</sup> macrophages in <em>CD274</em><sup><em>-/-</em></sup>; this was orthogonally verified, with the PD-L1 inhibitor BMS-1166 reducing macrophages to the same fold. Single-cell RNA sequencing further confirmed the down-regulation of the macrophage-defining transcription factors <em>SPI1</em> and <em>MAFB</em>. Furthermore, <em>CD274</em><sup><em>-/-</em></sup> macrophages reduced the level of inflammatory signals such as NF-κB and TNF, and chemokine secretion of the CXCL and CCL families. Anti-inflammatory TGF-β was up-regulated. Finally, we identified that <em>CD274</em><sup><em>-/-</em></sup> macrophages significantly down-regulated interferon-stimulated genes despite the presence of IFNγ in the differentiation media. These data suggest that PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells.</p> | - |
dc.language | eng | - |
dc.publisher | Life Science Alliance | - |
dc.relation.ispartof | Life Science Alliance | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.26508/lsa.202302461 | - |
dc.identifier.scopus | eid_2-s2.0-85176445683 | - |
dc.identifier.volume | 7 | - |
dc.identifier.issue | 2 | - |
dc.identifier.eissn | 2575-1077 | - |
dc.identifier.issnl | 2575-1077 | - |