Christopher P Cook, Mark Taylor, Yale Liu, Ralf Schmidt, Andrew Sedgewick, Esther Kim, Ashley Hailer, Jeffrey P North, Paymann Harirchian, Hao Wang, Sakeen W Kashem, Yanhong Shou, Timothy C McCalmont, Stephen C Benz, Jaehyuk Choi, Elizabeth Purdom, Alexander Marson, Silvia B V Ramos, Jeffrey B Cheng, Raymond J Cho
The homeostatic mechanisms that fail to restrain chronic tissue inflammation in diseases, such as psoriasis vulgaris, remain incompletely understood. We profiled transcriptomes and epitopes of single psoriatic and normal skin-resident T cells, revealing a gradated transcriptional program of coordinately regulated inflammation-suppressive genes. This program, which is sharply suppressed in lesional skin, strikingly restricts Th17/Tc17 cytokine and other inflammatory mediators on the single-cell level. CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, replicates the interleukin-17A (IL-17A), granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon gamma (IFNγ) elevation in psoriatic memory T cells deficient in these transcripts, functionally validating their influence...
August 16, 2022: Cell reports medicine