Extended Data Fig. 7: Loss of myeloid APC-derived IL-33 alters cutaneous immunity dependent on IL-17 and gd T cells.
(a), IL-17+ dermal γδ T cells were quantified in Langerin Cre-IL-33KO and control mice. Mean ± s.e.m (n = 4). (b), Dermal γδ T cells were evaluated in Foxp3Cre-ST2fl/fl and control mice. Mean ± s.e.m (n = 4,6). (c), Principal component analysis (PCA) of bulk RNA-seq of naïve skin explants from control or CD11c-IL-33KO mice. (d), Volcano plots of bulk RNA-seq analysis of differentially expressed genes from naïve skin explants from control or CD11c-IL-33KO mice. (e), Gene set enrichment analysis (GSEA) plots of pathways overrepresented by genes enriched in naïve skin from CD11c-IL-33KO mice. (f-h), Individual channels of IFA staining for Loricrin, Desmoglein-1 (Desm-1), or Ki-67 in skin sections from control or CD11c-IL-33KO mice. White arrows indicate localized areas of epidermal thickening. (i), IFA staining for Ki-67 in skin sections from control, Ctrl Ig-treated CD11c-IL-33KO, or CD11c-IL-33KO treated with neutralizing antibodies against IL-17 and IL-23. (j,k), Quantification of Ki-67+ and Krt5+ Ki-67+ cells in skin sections of control, CD11c-IL-33KO, or CD11c-IL-33KO treated with neutralizing antibodies against IL-17 and IL-23. Mean ± s.e.m (n = 12–15). (l), Quantification of epidermal thickness assessed by Loricrin- or Desmoglein-1 staining, as in D,E, of CD11c control, CD11c-IL-33KO, or CD11c-IL-33KO interbred with TCRδKO (CD11c-IL-33KO x TCRδKO) mice. Mean ± s.e.m (n = 12). (m,n), Percentage of non-penetrating S. mansoni cercariae quantified in Langerin Cre-IL-33KO or in Foxp3Cre-ST2fl/fl mice and compared with their respective controls. Mean ± s.e.m (n = 5,10). (o,p), CD11c-IL-33KO mice were treated with neutralizing antibodies against IFNγ for 10 days or interbred with TCRδKO mice (CD11c-IL-33KO x TCRδKO) prior to cercarial skin exposure. The proportion of non-penetrating cercariae was compared to CD11c control or CD11c-IL-33KO mice. Mean ± s.e.m (n = 6,8,18). P values were determined by two-tailed Student’s t-test or One-way ANOVA with post hoc correction. *P<0.05, **P<0.01, ***P<0.001. Representative of 2-3 independent experiments, each with ≥4 biological replicates.
