Blockade of Sema4a but not IFNαR1 signaling increases bronchiolitis severity and predisposes to subsequent asthma. (a) Protocol of PVM inoculation and administration of αSema4a or isotype control (IgG2a) and αIFNαR or isotype control (IgG1) to neonatal WT mice. (b) IFN-α protein expression in BALF, expressed as % change of the respective isotype control. (c) Viral load in the airway epithelium. (d) Nrp-1⁺ T reg cells in the lung. (e) IL-10 protein expression in lung, expressed as % change of the respective isotype control. (f) CD39 expression by Nrp-1⁺ T reg cells. (g) Sloughing of the airway epithelium. (h) Eosinophil number in BAL. (i) IL-33 protein expression in lung, expressed as % change of the respective isotype control. (j) Type-2 ILCs in lung. (k) AHR. (l) ASM area. (m) Intraluminal mucus plugging. (n) Eosinophil number in BAL. (o) IL-13 protein expression in BAL. Data are representative of n = 2 experiments with four to six neonates in each group and are presented as the mean ± SEM (k) or box-and-whisker plots showing quartiles (boxes) and range (whiskers; b–o). Data were analyzed by one-way (b–j and l–o) or two-way (k) ANOVA with Tukey’s post hoc test; *, P < 0.05; **, P < 0.01 compared with the respective isotype control–treated group or as indicated.