Extended Data Fig. 10: Inhibition of the JAK2-STAT5 pathway reduces the responsiveness of sensory neurons to allergens.
From: A γδ T cell–IL-3 axis controls allergic responses through sensory neurons
a, Representative fluorescence microscopic images of pSTAT5 in DRG neurons. The scale bar is 20 μm. b, Cumulative cheek scratch bouts following i.d. injection of papain or histamine (papain: n = 7 DMSO; n = 6 upad; histamine: n = 8 DMSO; n = 9 fed). c,e, Flow cytometric quantification of the draining lymph node (dLN) 24 h after immunization as indicated (c, n = 7 per group; e, n = 5 per group). d, Flow cytometric quantification of the draining lymph node (dLN) 5 days after immunization with ova ± papain (n = 8 DMSO ova; n = 12 DMSO ova+papain; n = 7 fedratinib ova; n = 12 fedratinib ova+papain). f, Graphical abstract: a γδ T cell-IL-3 axis controls allergic responses through sensory neurons. Vγ4+ GD3 cells are the major source of IL-3 in naïve skin and control the allergen responsiveness of Il3ra-expressing sensory neurons. Upon allergen exposure, IL-3-primed sensory neurons respond with robust itch, Th2-skewing DC migration to the dLN, and Th2 differentiation in the dLN. Mechanistically, IL-3 activates JAK2 and STAT5, leading to the transcription of the substance P gene Tac1. While JAK2 is necessary for allergic itch and the initiation of the allergic immune response, STAT5 is only required for the initiation of the allergic immune response. Together, the GD3-IL-3 axis controls the initial sensory neuronal response to allergens, dictating whether an organism is resistant or sensitive to allergens. Symbols represent individual mice (b,d), while symbols connected by lines indicate paired samples (c,e). Violin plots show the median and quartiles. Bar plots are mean ± SEM. Data are representative of at least two experiments and combined. Statistical tests: two-way repeated measures ANOVA (c,e), two-way ANOVA with Tukey’s multiple comparisons test (d), or two-sided unpaired t-test (b). * p < 0.05, ** p < 0.01, **** p < 0.0001, ns=not significant. Schematic in f created using BioRender (https://biorender.com).
