Navigating the blurred path of mixed neuroimmune signaling

Gupta, Surbhi; Viotti, Alice; Eichwald, Tuany; Roger, Anais; Kaufmann, Eva; Othman, Rahmeh; Ghasemlou, Nader; Rafei, Moutih; Foster, Simmie L.; Talbot, Sebastien

doi:10.1016/j.jaci.2024.02.006

Cited by 2 publications

References 176 publications

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Nociceptor Neurons Control Pollution-Mediated Neutrophilic Asthma

Wang,

Crosson,

Nikpoor

et al. 2024

Preprint

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The immune and sensory nervous systems, having evolved together, use a shared language of receptors and transmitters to maintain homeostasis by responding to external and internal disruptions. Although beneficial in many cases, neurons can exacerbate inflammation during allergic reactions, such as asthma. Our research modeled asthma aggravated by pollution, exposing mice to ambient PM2.5particles and ovalbumin. This exposure significantly increased bronchoalveolar lavage fluid neutrophils and γδ T cells compared to exposure to ovalbumin alone. We normalized airway inflammation and lung neutrophil levels by silencing nociceptor neurons at inflammation's peak using intranasal QX-314 or ablating TRPV1-expressing neurons. Additionally, we observed heightened sensitivity in chemical-sensing TRPA1 channels in neurons from pollution-exacerbated asthmatic mice. Elevated levels of artemin were detected in the bronchoalveolar lavage fluid from pollution-exposed mice, with artemin levels normalizing in mice with ablated nociceptor neurons. Upon exposure to PM2.5particles, alveolar macrophages expressing pollution-sensing aryl hydrocarbon receptors were identified as the source of artemin. This molecule enhanced TRPA1 responsiveness and increased neutrophil influx, providing a novel mechanism by which lung-innervating neurons respond to air pollution and suggesting a potential therapeutic target for controlling neutrophilic airway inflammation in asthma, a clinically intractable condition.

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Nociceptor Neurons Control Pollution-Mediated Neutrophilic Asthma

Wang,

Crosson,

Nikpoor

et al. 2024

Preprint

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Probiotic and high-fat diet: effects on pain assessment, body composition, and cytokines in male and female adolescent and adult rats

Raff,

Hainsworth,

Woyach

et al. 2024

American Journal of Physiology-Regulatory, Integrative and Comp

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Obesity in adolescence is increasing in frequency and is associated with elevated proinflammatory cytokines and chronic pain in a sex-dependent manner. Dietary probiotics may mitigate these detrimental effects of obesity. Using a Long-Evans adolescent and adult rat model of overweight (high fat diet - 45% kcal from fat from weaning; HFD), we determined the effect of a single strain dietary probiotic (L. plantarum 299v [Lp299v] from weaning) on the theoretically increased neuropathic injury-induced pain phenotype and inflammatory cytokines. We found that although HFD increased fat mass, it did not markedly affect pain phenotype, particularly in adolescence, but there were subtle differences in pain in adult male vs. female rats. The combination of HFD and Lp299v augmented the increase in leptin in adolescent females. There were many non-interacting, main effects of age, diet and probiotic on an array of cytokines and adipokines with adults being higher than adolescents, HFD higher than the control diet, and a decrease with probiotic compared to placebo. Of particular interest were the probiotic-induced increases in IL12p70 in female adolescents on a HFD. We conclude that a more striking pain phenotype could require a higher and longer duration caloric diet or different etiology of pain. A major strength of our study was that a single strain probiotic had a wide range of inhibiting effects on most pro-inflammatory cytokines. The positive effect of probiotic on leptin in female adolescent rats is intriguing and worthy of exploration.

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Navigating the blurred path of mixed neuroimmune signaling

Cited by 2 publications

References 176 publications

Nociceptor Neurons Control Pollution-Mediated Neutrophilic Asthma

Nociceptor Neurons Control Pollution-Mediated Neutrophilic Asthma

Probiotic and high-fat diet: effects on pain assessment, body composition, and cytokines in male and female adolescent and adult rats

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