Fig. 1: A previously unrecognized alternative promoter drives IL-33 receptor expression in antiviral T cells.
From: A type 1 immunity-restricted promoter of the IL−33 receptor gene directs antiviral T-cell responses
a, Scheme depicting the curated Il1rl1 gene. b, ST2 surface expression by in vitro differentiated T-cell subsets. Percentages in black, mean fluorescence intensity of ST2+ T cells in red. c, Il1rl1 first exon usage by differentiated T cells (CTL: n = 4 with one sample less than the limit of quantification (LOQ) in exon 1a and 1b reactions, Th1: n = 3, Th2: n = 4, NIH3T3: n = 2). d, RNA-seq coverage and splice junction tracks of ST2+ CTLs and Th1 and Th2 cells (n = 3 per subset) at the Il1rl1 locus. chr1:40,377,000–40,465,500; GRCm38.p6/mm10 is shown. e,f, WT mice received LCMV-specific P14 or Smarta T cells and were infected with LCMV-WE. P14 CTLs and Smarta Th1 cells were isolated on d7 p.i., and Il1rl1 first exon usage was analyzed by qPCR (e; CTL: n = 4 with two samples <LOQ in exon 1a reaction, Th1: n = 4, Th2 control (ctrl) (in vitro): n = 2) and RT-PCR (f). g, ChIP-seq tracks indicating T-bet36, STAT4 (ref. 38) and GATA-3 (ref. 37) binding and ATAC-seq tracks showing chromatin accessibility in naive or activated LCMV-specific T cells39,40. h, Computational pipeline to identify alternative TSSs between type 1- (CTL, Th1) and type 2- (Th2) polarized T cells. i, Manhattan plot showing identified hits (parameters minAbs = 0.25 and promoter fold change (FC) = 2, dashed line: P = 0.01). j, Heatmap of identified TSSs with P < 0.01 and their respective ProActiv-normalized expression across all replicates. In i and j, red texts are used to highlight the important transcriptional start sites detected. Data in panels c, e and f are representative of two independent experiments. Data are presented as mean ± standard deviation, with each dot representing T cells isolated from individual mice. P was determined using two-tailed t-tests with Benjamini–Hochberg (BH) correction (i and j).
