Fig. 3: Allergen-induced avoidance behaviour requires cysteinyl leukotrienes.
From: Immune sensing of food allergens promotes avoidance behaviour
a, Leukotriene biosynthetic pathway with targets of inhibitors and knockout mice in bold. b, Preference to OVA in OVA + alum-sensitized BALB/c mice. Zileuton was used as an ALOX5 inhibitor 1 h before the preference test (n = 8 vehicle control, 10 vehicle allergic, 5 zileuton control, 15 zileuton allergic). c, Alox5 expression across the gastrointestinal tract of control and OVA + alum-sensitized BALB/c mice after allergen oral challenges (n = 6 control and 8 allergic). d, Alox5 expression in the duodenum of OVA-sensitized WT, IgE-deficient or mast cell-depleted mice (n = 6 WT control, 8 WT allergic, 6 IgE-KO allergic, 4 MC-depleted allergic). e, Concentration of LTE4 per milligram of duodenal tissue determined by mass spectrometry in allergic WT and LTC4S-KO mice after oral challenges (n = 3 WT control, 5 WT allergic, 3 LTC4S-KO allergic). f,g, Cumulative licks of OVA (f; n = 9 WT allergic, 5 LTC4S-KO allergic) and OVA preference (g; n = 8 WT control, 13 WT allergic, 6 LTC4S-KO control, 8 LTC4S-KO allergic) of sensitized LTC4S-KO or BALB/c control mice. h, Preference to OVA in OVA + alum-sensitized mice. HAMI3379 was used as a CysLTR2 inhibitor 1 h before the preference test (first day of preference testing shown; n = 11 vehicle control, 7 vehicle allergic, 6 HAMI3379 control, 10 HAMI3379 allergic). i, OVA preference of sensitized CysLTR2-KO or BALB/c control mice during the first day of testing (n = 10 WT control and allergic, 6 CysLTR2-KO control, 8 CysLTR2-KO allergic). j, Schematic protocol for subdiaphragmatic vagotomy in OVA + alum-sensitized BALB/c mice. k, OVA preference was determined 3 weeks post vagotomy (vgx; n = 7 sham control, 7 sham allergic, 11 vagotomy control, 8 vagotomy allergic). Graphs show mean ± s.e.m. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. b,e,g–i,k, Two-tailed Man–Whitney test. c,d, One-way analysis of variance (ANOVA) with Tukey’s multiple-comparison test. Each panel is representative of at least two independent experiments. j, Created with BioRender.com.
