Fig. 3: Activation of PROKR2^ADV fibres drives the vagal–adrenal anti-inflammatory axis.

a, Schematic of optical stimulation of the ST36 acupoint in control and Prokr2^Adv-CatCh (CatCh) mice. Perios, periosteum. b, Images (left) and quantification (right) of Fos (green) induction in ChAT⁺ (red) DMV neurons (n = 5 mice; two-sided Student’s unpaired t-test, t₈ = 8.713, ***P < 0.001). Arrow, ChAT⁺ cells in DMV; arrowheads, Fos⁺ChAT⁺ neurons. c, Left, example vagal efferent electrical activity traces from CatCh and control mice. Right, CatCh mice exhibit increased firing compared with control mice (n = 5 mice per group; two-sided Student’s unpaired t-test, t₈ = 4.855, **P = 0.001). d, CatCh mice show loss of increased release of noradrenaline, adrenaline and dopamine induced by optical activation of PROKR2^ADV fibres following subdiaphragmatic vagotomy (sVX) compared with mice that underwent sham surgery. Two-way ANOVA, n = 6 mice, F_{1, 20} = 33.278 (NA), 33.188 (A), 80.020 (DA), P < 0.001; post hoc Tukey’s paired comparisons: ***P < 0.001; NS, P = 0.326 (NA), P = 0.584 (A) and P = 0.697 (DA). – denotes control littermates and + denotes CatCh mice. e, f, Optical activation of PROKR2^ADV fibres reduced LPS-induced production of TNF (e) and IL-6 (f) in mice that underwent sham surgery but not in sVX mice. Two-way ANOVA, n = 6 mice; for TNF: F_{1, 20} = 8.021, P < 0.001; for IL-6: F_{1, 20} = 10.695, P = 0.004; post hoc Tukey’s test: **P = 0.003 (TNF) or P = 0.001 (IL-6); NS, P = 0.535 (TNF) or P = 0.486 (IL-6). g, Optical activation of PROKR2^ADV fibres promoted survival in CatCh mice (n = 22 mice per group, two-sided log-rank test, ***P < 0.001). Scale bars, 100 μm. Data are mean ± s.e.m.