Journal article

Pharmacological validation of targets regulating CD14 during macrophage differentiation

Gisela Jimenez-Duran, Rosario Luque-Martin, Meghana Patel, Emma Koppe, Sharon Bernard, Catriona Sharp, Natalie Buchan, Ceara Rea, Menno PJ de Winther, Nil Turan, Davina Angell, Christine A Wells, Rick Cousins, Palwinder K Mander, Seth L Masters

EBioMedicine | ELSEVIER | Published : 2020

Abstract

The signalling receptor for LPS, CD14, is a key marker of, and facilitator for, pro-inflammatory macrophage function. Pro-inflammatory macrophage differentiation remains a process facilitating a broad array of disease pathologies, and has recently emerged as a potential target against cytokine storm in COVID19. Here, we perform a whole-genome CRISPR screen to identify essential nodes regulating CD14 expression in myeloid cells, using the differentiation of THP-1 cells as a starting point. This strategy uncovers many known pathways required for CD14 expression and regulating macrophage differentiation while additionally providing a list of novel targets either promoting or limiting this proce..

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Grants

Awarded by European Union


Funding Acknowledgements

This work was supported by a Viertel Senior Medical Research Foundation Fellowship (SLM) and the European Union's Horizon 2020 research and innovation program under Grant Agreement No. ITN-2014-EID-641665 [ITN-grant EPIMAC to MPJdW].