Fig. 3: Succinate-elicited IL-25 production in tuft cells is triggered by IP3R2.

a,b, Frequencies of small intestinal IL-13 (Sm13)+ (a) and Ki-67+ (b) ILC2s quantified by flow cytometry from Il25tdTomato; Itpr2–/– and Il25tdTomato; Itpr2+/– littermate mice treated with succinate for 4 days (n = 7–8 mice). c, Flow cytometry analysis of Il25tdTomato (Flare25) reporter and CD24 expression, gated on EpCAM+ cells. d, Il25 mRNA expression in tuft and nontuft epithelial cells sorted by fluorescence-activated cell sorting (FACS) from the proximal small intestine (n = 6–7 mice; ND, not detected in at least one sample). e,f, Frequencies of IL-13 (Sm13)+ (e) and Ki-67+ (f) ILC2s quantified by flow cytometry from Il25tdTomato; Itpr2–/– and Il25tdTomato; Itpr2+/– mice treated with 1 μg rIL-25 on two consecutive days (n = 11–12 mice). g, Mice expressing the IL-13 (Sm13) reporter were treated with succinate for 4 days and injected with PBS or an anti-IL-17RB blocking antibody on days 0 and 2. h,i, Frequencies of IL-13 (Sm13)+ (h) and Ki-67+ (i) ILC2s quantified by flow cytometry (n = 5–6 mice). Data are indicated as mean or mean ± s.e.m (a, b, d–f, h–i). Data were analyzed using a two-way analysis of variance (ANOVA) (a, b), a one-way ANOVA (h, i) or the Mann–Whitney test (e, f). *P = 0.01–0.05; **P = 0.01–0.001; ****P < 0.0001; NS, P ≥ 0.05.