Abstract
Chemical biology provides an attractive approach to identify genes involved in a particular biological process. This screening approach has its advantages because the assays are usually non-destructive, and analysis can be performed even if the mechanism of action is unknown. During an immune reaction, cells upregulate the expression and secretion of small proteins called cytokines that have specific effects on the interactions and communication between cells. Here, we describe the principles and steps involved in the execution of chemical screening for identifying epigenetic inhibitors that affect cytokine production in differentiated Th1, Th2, and Th17 cells. Our approach provides a rationale for identifying epigenetic chemical compounds that are capable of controlling CD4+ T-cell cytokine function that may be beneficial for treating inflammatory diseases.
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References
Khersonsky SM, Chang YT (2004) Forward chemical genetics: library scaffold design. Comb Chem High Throughput Screen 7(7):645–652
Zheng W, Thorne N, McKew JC (2013) Phenotypic screens as a renewed approach for drug discovery. Drug Discov Today 18(21–22):1067–1073
Choi H et al (2014) Forward chemical genetic screening. Methods Mol Biol 1062:393–404
Chen GQ et al (2019) Phenotype and target-based chemical biology investigations in cancers. Natl Sci Rev 6(6):1111–1127
Cribbs AP et al (2020) Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism. Proc Natl Acad Sci U S A 117(11):6056–6066
Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11(11):762–774
Skapenko A et al (2005) The role of the T cell in autoimmune inflammation. Arthritis Res Ther 7(Suppl 2):S4–S14
Sandquist I, Kolls J (2018) Update on regulation and effector functions of Th17 cells. F1000Res 7:205
Samotij D, Reich A (2019) Biologics in the treatment of lupus erythematosus: a critical literature review. Biomed Res Int 2019:8142368
Cottone L et al (2020) Inhibition of histone H3K27 demethylases inactivates Brachyury (TBXT) and promotes Chordoma cell death. Cancer Res 80(20):4540–4551
Ebrahimi A et al (2019) Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming. Nat Chem Biol 15(5):519–528
Ugurlu-Cimen D et al (2021) AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation. Epigenetics Chromatin 14(1):32
Acknowledgements
This work was supported through Innovate UK (UO, APC), the National Institute for Health Research Oxford Biomedical Research Centre (UO), Cancer Research UK (CRUK, UO), the Bone Cancer Research Trust (APC and UO), the Leducq Epigenetics of Atherosclerosis Network (LEAN) program grant from the Leducq Foundation (UO), the Chan Zuckerberg Initiative (APC), and the Myeloma Single Cell Consortium (UO). APC is a recipient of an MRC Career Development Fellowship (MR/V010182/1).
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Cribbs, A.P., Oppermann, U. (2023). Phenotypic Chemical Screening in CD4+ T Cells to Identify Epigenetic Inhibitors. In: Merk, D., Chaikuad, A. (eds) Chemogenomics. Methods in Molecular Biology, vol 2706. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3397-7_17
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DOI: https://doi.org/10.1007/978-1-0716-3397-7_17
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