Fig. 7: CD39⁺CD9⁺ IMs from PBS/PBS or OVA + LPS/OVA + αIL-23p19 suppress Th17-mediated neutrophilic inflammation in NDA mice.

a Schematic diagram of the adoptive transfer protocol. CD39⁺CD9⁺ IMs were sorted from OVA + LPS/OVA + αIL-23p19 or PBS/PBS, while Ly6G⁺CD39⁺CD9⁺ neutrophils were sorted from PBS/PBS on day 24. These isolated cells were intravenously transferred on every challenge to the NDA mouse model. The inflammatory response was assessed at 48 hr after the last challenge. b Total cell and neutrophil counts in BALF. c Percentages of Ly6G⁺ neutrophils (b, c; n = 9 per group). d RORγt⁺ Th cells in CD4⁺ T cells in the lung. e Levels of IL-17 and IL-22 in BALF (d, e; Vehicle (PBS) → NDA mice (n = 10), CD39⁺CD9⁺ IM (OVA + LPS/OVA+αIL23p19)→NDA mice (n = 10), CD39⁺CD9⁺ IM (PBS/PBS) → NDA mice (n = 6), and Ly6G⁺CD39⁺CD9⁺ neutrophil IM (PBS/PBS) → NDA mice (n = 6)). f IL-23 in BALF (n = 3 per group). g Representative images of H&E staining and (h) inflammatory scores quantified from H&E staining (n = 6 per group). Scale bar = 100 μm. i P_enh values were measured using a whole body plethysmography. (Vehicle (PBS) → NDA mice (n = 10), CD39⁺CD9⁺ IM (OVA + LPS/OVA+αIL23p19)→NDA mice (n = 10), CD39⁺CD9⁺ IM (PBS/PBS) → NDA mice (n = 6), and Ly6G⁺CD39⁺CD9⁺ neutrophil IM (PBS/PBS) → NDA mice (n = 6)). j Representative images of lung immunostaining for citH3 (red), MPO (green), and DAPI (blue). The citH3⁺MPO⁺ NETs are shown in yellow. k Colocalization area (µm²) of citH3⁺MPO⁺ NETs (n = 17 per group). Scale bar = 20 μm. l Violin plots showing distributions of the signature scores of TREM2^high CM in patients with mild/moderate (n = 30) and severe asthma (n = 33) in the SARP cohort. Center line, median value. Data are shown as mean ± s.e.m. Significance was determined by one-way ANOVA with Tukey’s post hoc correction (b–f, h, k), two-way ANOVA with Sidak’s post hoc correction (i), and one-tailed Student’s t test (l).