496 Differential chromatin accessibility and gene expression suggest Th17 polarization in activated and skin-homing T cells
نویسندگان
چکیده
We generated 1,090 ATAC-seq and 1,057 T-cell RNA-seq libraries from 153 subjects, derived 8 flow-sorted subsets (defined by CD4/CD8, CLA+/ CLA-, 0/24h CD3/CD28 stimulation). Effects of activation skin-homing were analyzed DESeq2. After peak calling, 78,234 consensus peaks present in ≥ 30 libraries. A Wald test examining simple main effects identified 9,072, 3,934, 21,174 as differentially accessible regions (DAR; FDR < 0.05, |log2 FC|≥ 0.585) CD4 vs CD8, CLA+ resting vs. activated T-cells, respectively. For functional annotation, DARs assigned to the closest genes using ChIPseeker. CD4/CD8 most significantly enriched for KEGG pathway “Th17 cell differentiation” (FDR=2.4e-07). CLA+/CLA- “MAPK signaling pathway” (FDR=1.5e-06) included (FDR=4.1e-04). Activation-responsive (0/24h) “T receptor (FDR = 1.0e-07) (FDR=2.3e-06). used same criteria identify expressed (DEGs) libraries, yielding 2,795, 3,629, 10,673 CD8/CD4, CLA+/CLA-, 0/24h, DEGs revealed top enrichment “Cytokine-cytokine interaction (CCRI)” 8.3e-19) 7.8e-03), with up-regulation IL17A (3.2-fold), IL17F (1.8-fold), IL22 (2.9-fold) CD4. also “CCRI” (FDR=2.4e-18), (3.3-fold), (2.2-fold), (1.9-fold) CLA+. 2.1e-04), dramatic (109-fold), (1052-fold), (146-fold) at 24 h. IL17A, IL17F, among 479 DAR/DEG pairs both comparisons, IL23R was 1 66 all 3 comparisons. These results support a link between Th17 polarization.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.05.505