Roles of Bronchopulmonary C-fibers in airway Hyperresponsiveness and airway remodeling induced by house dust mite

Abstract

BackgroundAsthma is characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling. While exposure of house dust mites (HDM) is a common cause of asthma, the pathogenesis of the HDM-induced asthma is not fully understood. Bronchopulmonary C-fibers (PCFs) contribute to the neurogenic inflammation, viral infection induced-persistent AHR, and ovalbumin induced collagen deposition largely via releasing neuropeptides, such as substance P (SP). However, PCF roles in the pathogenesis of the HDM-induced asthma remain unexplored. The goal of this study was to determine what role PCFs played in generating these characteristics.MethodsWe compared the following variables among the PCF-intact and -degenerated BALB/c mice with and without chronic HDM exposure (four groups): 1) AHR and pulmonary SP; 2) airway smooth muscle (ASM) mass; 3) pulmonary inflammatory cells; and 4) epithelium thickening and mucus secretion.ResultsWe found that HDM evoked AHR associated with upregulation of pulmonary SP and inflammation, ASM mass increase, epithelium thickenings, and mucus hypersecretion. PCF degeneration decreased the HDM-induced changes in AHR, pulmonary SP and inflammation, and ASM mass, but failed to significantly affect the epithelium thickening and mucus hypersecretion.ConclusionOur data suggest an involvement of PCFs in the mechanisms by which HDM induces allergic asthma via airway inflammation, AHR, and airway remodeling.

Neuroimmune regulatory networks of the airway mucosa in allergic inflammatory disease

“…2A). In particular, in an allergic‐like asthma model induced by HDM exposure, elevated levels of pulmonary SP are detected, however denervation of bronchopulmonary C fibers profoundly reduces evoked AHR, correlating with a significant reduction in pulmonary SP 28 …”

“…C‐fiber neuronal innervation is much denser in asthmatic patients and these neurons exhibit hyperexcitability 26,27 . Further, neuronal TRPV1 expression can be increased following exposure to ozone in the ovalbumin (OVA)‐induced murine asthma model 27 and TRPV1+ c‐fiber ablation alleviates house dust mite (HDM)‐induced lung inflammation 28 . Genetic deficiency or antagonism of TRPA1 can prevent immune cell infiltration and airway hypercontraction 29 .…”

Vagal‐α7nAChR signaling attenuates allergic asthma responses and facilitates asthma tolerance by regulating inflammatory group 2 innate lymphoid cells

“…PCFs are capsaicin‐sensitive nerves, and recent studies have revealed that degeneration of PCFs by capsaicin pretreatment but not downstream receptor TRPV1 (transient potential receptor vanilloid 1) blockade can decrease allergic airway inflammatory responses, including eosinophils, Th2 cells and inflammatory cytokines, as well as reduce asthmatic hyperreactivity and airway remodeling in an asthma model 30,32,33,40,41 . However, whether PCFs have effects on ILC2s, especially iILC2s, in asthma and tolerance is not very clear.…”

“…Previous studies have shown that vagotomy, PCF degeneration or α7nAChR activation can alleviate allergen‐induced airway hyperreactivity and reduce allergic airway inflammation in asthma models, including eosinophils and Th2 cells infiltration and inflammatory cytokines production 14,30,32,33,35,36,40,41 . Consequently, our research has a minor flaw in that we mainly focused on changes in ILC2 numbers.…”

Long Noncoding RNAs in the Regulation of Asthma: Current Research and Clinical Implications

“…It was found that ASMCs proliferation was aggravated in asthmatic patients and there were more ASMCs from asthma subjects than from healthy subjects in post-mortem airway sections (Fujita et al, 2011;Elliot et al, 2018;James et al, 2018). In vivo, ASMCs thickening and proliferation were verified to be promoted in house dust mite-induced murine (Yang et al, 2017). Reversely, the diminish of ASMCs could restore bronchial airway thickening of the murine, leading to the relief of airway remodeling (Kohan et al, 2009).…”