Journal: eLife

Article Title: Nociceptor neurons control pollution-mediated neutrophilic asthma

doi: 10.7554/eLife.101988

Figure Lengend Snippet: ( A – B ) Male and female C57BL/6 mice (6–10 weeks of age) were sensitized intraperitoneally with ovalbumin (OVA; 200 µg/dose in 200 µl) and aluminum hydroxide (1 mg/dose in 200 µl) on days 0 and 7. On days 14–16, mice were challenged intranasally with OVA (50 µg/dose in 50 µl) alone or with fine particulate matter (FPM; 20 µg/dose in 50 µl). On day 16, 30 min after the final challenge, mice received intranasal QX-314 (5 nmol/dose in 50 µl). Bronchoalveolar lavage fluid (BALF) was collected on day 17 and analyzed by flow cytometry. Compared with naïve or OVA-exposed mice, those co-challenged with OVA+FPM showed increased BALF neutrophils ( A ). QX-314 treatment normalized these levels, while BALF eosinophil levels remained comparable ( B ). ( C – E ) Male and female littermate control (TRPV1 WT ) and nociceptor-ablated (TRPV1 DTA ) mice (6–10 weeks of age) were sensitized and challenged under the same OVA±FPM protocol (days 0, 7, and 14–16). BALF or lungs were collected on day 17 and assessed by flow cytometry. Compared with naïve or OVA-exposed mice, OVA+FPM co-challenged mice exhibited higher BALF neutrophils ( C ) and lung γδ T cells ( E ). Nociceptor ablation protected against these increases ( C, E ), while BALF eosinophil levels remained comparable ( D ). Data are shown as mean ± SEM ( A – E ). Experiments were replicated twice, and animals pooled ( A–E ). N are as follows: ( A–B ) control (n=6), OVA (n=7), OVA-FPM (n=12), OVA-FPM+QX-314 (n=10), ( C–D ) TRPV1 WT + control (n=9), TRPV1 WT + OVA (n=13), TRPV1 WT + OVA-FPM (n=18), TRPV1 DTA + OVA-FPM (n=19), ( E ) TRPV1 WT + control (n=3), TRPV1 WT + OVA (n=3), TRPV1 WT + OVA-FPM (n=4), TRPV1 DTA + OVA-FPM (n=5). p-Values were determined by a one-way ANOVA with post hoc Tukey’s ( A–E ). p-Values are shown in the figure.

Article Snippet: In some experiments, QX-314 (Tocris, #1014; 5 nmol in 50 μl) or PBS was administered intranasally on day 16 to control asthmatic mice (as detailed in the asthma protocol).

Techniques: Flow Cytometry, Control

Journal: eLife

Article Title: Nociceptor neurons control pollution-mediated neutrophilic asthma

doi: 10.7554/eLife.101988

Figure Lengend Snippet: In our study, mice were exposed to PM 25 particles and ovalbumin (OVA) to model pollution-exacerbated asthma. Compared to mice exposed to OVA alone, co-exposure to PM 25 and OVA significantly increased bronchoalveolar lavage fluid (BALF) neutrophils and lung γδ T cell levels. To counteract this heightened airway inflammation, we administered intranasal QX-314—a charged lidocaine derivative—at the peak of inflammation, effectively normalizing BALF neutrophil levels. Ablation of TRPV1 + nociceptor neurons produced a similar effect. Further analysis with calcium imaging revealed that neurons from the jugular-nodose complex in pollution-exposed asthmatic mice were more sensitive via their TRPA1 channels. Levels of TNFα and the growth factor artemin were also elevated in the BALF of these mice, returning to normal following nociceptor ablation. We identified alveolar macrophages as the source of artemin, which they secrete upon sensing fine particulate matter (FPM) through aryl hydrocarbon receptors. Artemin, in turn, heightened TRPA1 responsiveness to its agonist (mustard oil), thereby exacerbating airway inflammation. Our findings suggest that silencing nociceptor neurons can disrupt this pathway, offering a novel therapeutic approach to mitigate neutrophilic airway inflammation driven by pollution.

Article Snippet: In some experiments, QX-314 (Tocris, #1014; 5 nmol in 50 μl) or PBS was administered intranasally on day 16 to control asthmatic mice (as detailed in the asthma protocol).

Techniques: Produced, Imaging