Neuro-immune mechanisms of visceral and airway hypersensitivity.

Both the airways and the intestine are continuously exposed to antigens of microbial, nutritional and environmental origin.Recognition of harmless versus threatening antigens by the immune system is of crucial importance to maintain immune homeostasis thereby preventing an excessive immune response with subsequent tissue damage and impaired organ function.In line, the epithelial barrier tightly regulates the exposure of foreign antigens to the immune system to guarantee proper function of the immune system. Hence, increased permeability of the epithelial barrier will lead to increased exposure of foreign antigens and immune-mediated dysfunction of the intestine and airways, as in inflammatory bowel disease and asthma.Additionally, neuromuscular function can also be hampered by increased exposure of intraluminal antigens in the absence of overt inflammation.In patients with irritant-induced airway disease and functional bowel disorders, increased pain perception, enhanced mucus secretion and mucosal hyper responsiveness are observed without signs of overt inflammation.In the present project, we hypothesize that this so-called airway and visceral hypersensitivity results from increased access of foreign or environmental antigens to the submuscal/ subepithelial compartment due to impaired barrier function. Besides a genetic basis for increased permeability, the latter can be induced be environmental or microbial agents ultimately leading to direct or indirect activation of mast cells. These immune cells will release mediators that impair neuromuscular function an induce airway and visceral hypersensitivity characteristic of the diseases of interest.

Keywords:Ultrafine particles, Afferent nerve fibers, TRP channels, Airway Hyperreactivity, Mast cells, Visceral hyprsensityvity

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences