Figure 6. STAT-dependent Th9 bystander activation promotes allergic disease and is associated with responsiveness to JAK inhibitors.

a-c. Representative periodic acid-Schiff (PAS) stained images (a), pooled histology scores (b), and live CD45.1⁺TCRβ⁺CD4⁺CD44⁺IL-9⁺ (adoptively transferred Th9) cell counts (c) in lungs of WT mice who underwent adoptive transfer of PBS or Th9 cells from congenic donors, followed by intratracheal and intranasal challenge with PBS or IL-2 + IL-4; 3 replicates, n = 2 per replicate; arrows, inflammatory infiltrate; triangles, mucus. d-f. Representative PAS-stained images (d), pooled histology scores (e), and live CD45⁺TCRβ⁺CD4⁺CD44⁺IL-9⁺ (Th9) cell counts (f) from lungs of mice exposed to chronic papain-induced airway inflammation and treated with methylcellulose (MC) or tofacitinib; n = 6 (PBS/MC), n = 5 (PBS/tofa), n = 11 (Papain/MC), n = 10 (Papain/tofa); arrows, inflammatory infiltrate; triangles, mucus. In vivo data are shown as mean ± SEM, Mann-Whitney. g. Bar graph shows RMA-normalized IL9 expression in house dust mite (HDM) treated CD4⁺ T cells from healthy volunteers vs. patients with allergic disease. Scatterplot shows normalized enrichment scores (NES; Gene Set Enrichment Analysis, GSEA) and FDR for genes induced by the following TFs in allergic vs. healthy CD4⁺ cells: STAT1; STAT3; STAT4; STAT5; STAT6. h. Bar graph shows RMA-normalized IL9 expression in HDM-treated CD4⁺ T cells from allergic patients in which IL9 expression is lower than mean expression for the dataset (IL9^low) vs. higher than mean for the dataset (IL9^high). Scatterplot shows NES (GSEA) and FDR for genes induced by STAT1, STAT3, STAT4, STAT5, and STAT6 in IL9^low vs. IL9^high CD4⁺ cells. i. GSEA plots show NES and FDR for STAT5- and STAT6-induced genes in d29 vs. d0 skin from AD patients treated with the JAK-SYK inhibitor ASN002, 80 mg daily. All statistical tests are 2-sided; all replicates are biologically independent samples.