Image_2_Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration.TIF
Programmed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1 mRNA is abundant in many tissues. To address this puzzle, we investigated the function of PD-L1 in mammary gland development. Interestingly, we found that PD-L1 is enriched in protein C receptor (Procr)-expressing mammary stem cells (MaSCs), and PD-L1-expressing mammary basal cells (PD-L1+ basal cells) exhibit robust mammary regeneration capacity in transplantation assay. The lineage tracing experiment showed that PD-L1+ cells can differentiate into all lineages of mammary epithelium cells, suggesting that PD-L1+ basal cells have the activities of MaSCs. Furthermore, PD-L1 deficiency significantly impairs mammary development and reduces mammary regeneration capacity of mammary basal cells, suggesting that PD-L1 is not only enriched in MaSCs but also improves activities of MaSCs. In summary, these results demonstrated that PD-L1 is enriched in MaSCs and promotes mammary gland development and regeneration. Mechanistically, our data indicated that PD-L1 expression is induced by continuous activation of Wnt/ß-catenin signaling. In conclusion, these results demonstrated that PD-L1 is a marker of MaSCs, and PD-L1 is essential for mammary development. Our study provides novel insight into the physiological functions of PD-L1 in tissue development.
History
References
- https://doi.org//10.1186/s12943-015-0421-2
- https://doi.org//10.1002/eji.200425405
- https://doi.org//10.1289/ehp.898085
- https://doi.org//10.4049/jimmunol.170.3.1257
- https://doi.org//10.1016/j.stem.2016.11.007
- https://doi.org//10.1038/s41388-019-0700-2
- https://doi.org//10.1126/science.aan4153
- https://doi.org//10.1038/nri1349
- https://doi.org//10.1021/bp049865x
- https://doi.org//10.1038/nm863
- https://doi.org//10.1007/978-1-4615-9032-3_1
- https://doi.org//10.1002/path.4096
- https://doi.org//10.1038/nm730
- https://doi.org//10.1038/70932
- https://doi.org//10.1016/s1074-7613%2804%2900050-0
- https://doi.org//10.1158/2159-8290.CD-18-1259
- https://doi.org//10.1084/jem.192.7.1027
- https://doi.org//10.1158/2326-6066.cir-17-0537
- https://doi.org//10.1242/dev.087643
- https://doi.org//10.4049/jimmunol.1502291
- https://doi.org//10.1126/science.aaf0683
- https://doi.org//10.1242/dev.125.10.1921
- https://doi.org//10.1002/dvdy.20978
- https://doi.org//10.1073/pnas.0307252101
- https://doi.org//10.4049/jimmunol.169.7.3581
- https://doi.org//10.1002/dvg.20335
- https://doi.org//10.4049/jimmunol.176.4.2238
- https://doi.org//10.1126/science.1131000
- https://doi.org//10.1007/s10911-017-9372-0
- https://doi.org//10.1038/nrc3239
- https://doi.org//10.1038/nature12948
- https://doi.org//10.1182/blood-2004-09-3458
- https://doi.org//10.1038/nri.2017.108
- https://doi.org//10.1038/nature04496
- https://doi.org//10.1016/j.immuni.2018.03.014
- https://doi.org//10.1126/scitranslmed.3003689
- https://doi.org//10.1158/0008-5472.CAN-11-3379
- https://doi.org//10.1016/0092-8674%2888%2990220-6
- https://doi.org//10.1016/j.stem.2012.05.023
- https://doi.org//10.1038/nature10573
- https://doi.org//10.1038/nature13851
- https://doi.org//10.1038/s41422-019-0225-9
- https://doi.org//10.1016/j.canlet.2019.02.022
- https://doi.org//10.1038/nrd3877
- https://doi.org//10.1038/s41586-020-2631-z
- https://doi.org//10.1016/j.stem.2010.03.020
- https://doi.org//10.1038/nri2326