Immune cells and molecules, as well as synaptic transmission molecules play a regulatory role in the communication pathways of the entire body when it is necessary to engage all body resources in the fight against infections or tumor cells wherever they appear. In potential allergy, the neuroimmune network controls allergen tolerance maintenance at both local and systemic levels.The review focuses on different neurotransmitters and our understanding of a balance and imbalance between the immune system and the nervous system in allergic inflammation, including allergic rhinitis. However, the pathogenesis of the two endotypes of rhinitis (conventional allergic rhinitis and local allergic rhinitis) and the impact of the neuroimmune network on it remain unresolved.

Local allergic rhinitis, a new endotype of allergic rhinitis discerned by researchers of the Spanish Allergy School, is now in the focus of interest of international allergological community. A special feature of local allergic rhinitis, which, being similar to conventional signs of allergic rhinitis, is, however, characterized by absence of systemic atopy manifestations, e.g., an increased total serum IgE content and positive allergic skin tests. In order to assess the level of tolerance breakdown to allergens in local and classical allergic rhinitis, we have studyed concentrations of IL-4, IL-22, and IFNγ in three biological fluids, blood, nasal secretions, and skin exudate. The whole study cohort consisted of 82 patients aged 18 to 60 years with established allergic rhinitis. The diagnosis was based on counseling by allergologist/immunologist, including clinical case history and possible inheritance of atopy as well as videorhinoscopy performed by an ENT specialist. The procedure of videorhinoscopy allowed to specify allergic origin of rhinitis and exclude the patients with non-allergic forms of the disease, but it did not enable us to differentiate between the endotypes of classic and local allergic rhinitis. Subsequently, all patients have been divided into two subgroups based on the criteria of systemic atopy: (1) with a high content of serum total IgE and positive skin allergy tests (n = 41) and (2) with a significantly lower concentration of IgE and negative allergy tests (n = 41). It was concluded that the patients with classic allergic rhinitis prevailed in the 1st subgroup, whereas local rhinitis predominated in the 2nd group. The study of IL-4, IL-22 and IFNγ concentrations in the three biological fluids allowed us to presume that the 1st subgroup was characterized by increased content of IL-4 and IL-22 in blood and skin exudate in comparison with controls, and the 2nd subgroup showed a decrease in IFNγ to control values. The cytokine concentrations in nasal secretions were not representative for the subgroups studied. The result has been interpreted as the absence of tolerance breakdown to causal allergens in the patients with local allergic rhinitis at the systemic level. The obtained data could be used in development of a diagnostic biomarker system for this specific endotype of allergic rhinitis, thus avoiding potential diagnostic errors which occurred in the past, when this endotype was classified as non-allergic form of the disease, thus administering non-adequate treatment, e.g., allergen-specific immunotherapy, which could be prescribed in these cases.

The review considers the molecular structure of inflammasomes, routes of inflammasome activation, appropriate downstream effects, and their association with autoinflammatory, autoimmune, neurodegenerative, and allergic diseases and malignancies with a focus on the involvement of the skin in these pathologies. Inflammasome activation is interpreted as an early pathophysiological event before the onset of inflammation, and, especially, if inflammasome dysregulation occurs. All research aspects related to the NLRP3 inflammasome are described in detail. The review also considers promising directions for therapeutic interventions in NLRP3-associated diseases.

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