PT  - JOURNAL ARTICLE
AU  - Cao, Handi
AU  - Xiang, Yang
AU  - Zhang, Shihui
AU  - Chao, Yiming
AU  - Guo, Jilong
AU  - Aurich, Theo
AU  - Ho, Joshua WK
AU  - Huang, Yuanhua
AU  - Liu, Pentao
AU  - Sugimura, Ryohichi
TI  - PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells
AID  - 10.26508/lsa.202302461
DP  - 2024 Feb 01
TA  - Life Science Alliance
PG  - e202302461
VI  - 7
IP  - 2
4099  - https://www.life-science-alliance.org/content/7/2/e202302461.short
4100  - https://www.life-science-alliance.org/content/7/2/e202302461.full
SO  - Life Sci. Alliance2024 Feb 01; 7
AB  - 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.