The prevalence of conventional and new pathogenic types of allergies is increasing. For the last few years, new atopic disorders -local allergic rhinitis (LAR), local allergic asthma, "dual" allergic rhinitis, and local allergic conjunctivitis -have been described. In particular, LAR was identified a decade ago, whereas its immunopathogenesis is still unclear. Nevertheless, the network of immune cells and neurons determining the maintenance or breakdown of allergen tolerance has partially been studied. Therefore, this field of research is currently at the cutting edge. However, there is still not any definitive answer as to why local disorders take place. Specifically, the nasal cavity is characterized by the following prevalent neuro molecules: acetylcholine, norepinephrine, substance P, neuromedin U, vasoactive intestinal peptide, and calcitonin-gene-related peptide; some of which are pro-immunogenic and a slightly smaller part is protolerogenic. In the spotlight, the hypothesis of an autonomous breakdown of tolerance to allergens in LAR is presented. The article describes immune tolerance as the antipode of the active immune response, which does not lead to producing effector cells and molecules, and vice versa is based on active immunosuppressive processes. In addition, this article focuses on the mechanisms of the maintenance and breakdown of allergen tolerance, a form of immune tolerance, at the nasal level and throughout the body, and the essential role of various cells and molecules, including neuro molecules, in the pathogenesis of LAR.

Immune cells and immune-derived molecules, endocrine glands and hormones, the nervous system and neuro molecules form the combined tridirectional neuroimmune network, which plays a significant role in the communication pathways and regulation at the level of the whole organism and local levels, in both healthy persons and patients with allergic rhinitis based on an allergic inflammatory process. This review focuses on a new research paradigm devoted to neuronal-immune cell units, which are involved in allergic inflammation in the nose and neuroimmune control of the nasal mucociliary immunologically active epithelial barrier. The categorization, cellular sources of neurotransmitters and neuropeptides, and their prevalent profiles in constituting allergen tolerance maintenance or its breakdown are discussed. Novel data on the functional structure of the nasal epithelium based on a transcriptomic technology, single-cell RNA-sequencing results, are considered in terms of neuroimmune regulation. Notably, the research of pathogenesis and therapy for atopic allergic diseases, including recently identified local forms, from the viewpoint of the tridirectional interaction of the neuroimmune network and discrete neuronal-immune cell units is at the cutting-edge.

Представлен обзор современных исследований, посвященных недавно открытому явлению-феномену энтопии (локальной атопии), с точки зрения его фенотипов и эндотипов. Клиническим вариантом эндотипа энтопии является локальный аллергический ринит, новая патология,-объект исследований в современной иммунологии, аллергологии и оториноларингологии. Точные механизмы срыва толерантности к аллергенам при энтопии остаются неясными. Между тем феномен энтопии может стать ключом для расшифровки нерешенных вопросов срыва аллергической толерантности в разных анатомических сайтах. Обзор посвящен патогенезу, диагностическому алгоритму и проблеме выбора терапевтических подходов при локальном аллергическом рините. Ключевые слова: aллергены, aтопия, энтопия, толерантность к аллергенам, aллергический ринит, локальный аллергический ринит, фенотипы, эндотипы, биомаркеры, Т-хелперы 2-го типа, T-регуляторные клетки. Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи. Источник финансирования. Авторы заявляют об отсутствии финансирования.

Allergen tolerance is an active physiological process, which runs opposite to the adaptive immune response. The induction of allergen tolerance involves the multiple regulatory networks of cells and biomolecules. There are T regulatory cells, tolerogenic dendritic cells, IL10, IL35, TGFb, and immunosuppressive neurotransmitters. of this review is the overview of allergen tolerance mechanisms and its breakdown at the systemic and local levels, particularly concerning such specific organ as the nose. In this review, immune tolerance is initially considered on the whole. Then the review focuses on mechanisms of the physiological

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.