{"title":"Neuroimmune mechanisms of type 2 inflammation in the skin and lung.","authors":"Masato Tamari, Aaron M Ver Heul","doi":"10.1016/j.alit.2025.02.001","DOIUrl":null,"url":null,"abstract":"<p><p>Type 2 inflammation has a major role in barrier tissues such as the skin and airways and underlies common conditions including atopic dermatitis (AD) and asthma. Cytokines including interleukin 4 (IL-4), IL-5, and IL-13 are key immune signatures of type 2 inflammation and are the targets of multiple specific therapeutics for allergic diseases. Despite shared core immune mechanisms, the distinct structures and functions of the skin and airways lead to unique therapeutic responses. It is increasingly recognized that the nervous system has a major role in sensing and directing inflammatory processes. Indeed, crosstalk between type 2 immune activation and somatosensory functions mediates tissue-specific signatures such as itching in the skin. However, neuroimmune interactions are shaped by distinct neuronal and immune landscapes, and differ between the skin and airways. In the skin, dorsal root ganglia-derived neurons mediate pruritus via type 2 cytokines and neurogenic inflammation by mast cell or basophil activation. Conversely, vagal ganglia-derived neurons regulate airway immune responses by releasing neuropeptides/neurotransmitters such as calcitonin gene-related peptides, neuromedin U, acetylcholine, and noradrenaline. Sensory neuron-derived vasoactive intestinal peptide forms a feedback loop with IL-5, amplifying eosinophilic inflammation in the airways, a mechanism that is absent in the skin. These differences influence the efficacy of cytokine-targeted therapies. For instance, IL-4/IL-13-targeted therapies like dupilumab demonstrate efficacy in AD and allergic airway diseases, whereas IL-5-targeted therapies are effective in eosinophilic asthma but not AD. Understanding these neuroimmune interactions underscores the need for tailored therapeutic approaches to address allergic diseases where barrier tissues are involved.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2000,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergology International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.alit.2025.02.001","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
Neuroimmune mechanisms of type 2 inflammation in the skin and lung.
Type 2 inflammation has a major role in barrier tissues such as the skin and airways and underlies common conditions including atopic dermatitis (AD) and asthma. Cytokines including interleukin 4 (IL-4), IL-5, and IL-13 are key immune signatures of type 2 inflammation and are the targets of multiple specific therapeutics for allergic diseases. Despite shared core immune mechanisms, the distinct structures and functions of the skin and airways lead to unique therapeutic responses. It is increasingly recognized that the nervous system has a major role in sensing and directing inflammatory processes. Indeed, crosstalk between type 2 immune activation and somatosensory functions mediates tissue-specific signatures such as itching in the skin. However, neuroimmune interactions are shaped by distinct neuronal and immune landscapes, and differ between the skin and airways. In the skin, dorsal root ganglia-derived neurons mediate pruritus via type 2 cytokines and neurogenic inflammation by mast cell or basophil activation. Conversely, vagal ganglia-derived neurons regulate airway immune responses by releasing neuropeptides/neurotransmitters such as calcitonin gene-related peptides, neuromedin U, acetylcholine, and noradrenaline. Sensory neuron-derived vasoactive intestinal peptide forms a feedback loop with IL-5, amplifying eosinophilic inflammation in the airways, a mechanism that is absent in the skin. These differences influence the efficacy of cytokine-targeted therapies. For instance, IL-4/IL-13-targeted therapies like dupilumab demonstrate efficacy in AD and allergic airway diseases, whereas IL-5-targeted therapies are effective in eosinophilic asthma but not AD. Understanding these neuroimmune interactions underscores the need for tailored therapeutic approaches to address allergic diseases where barrier tissues are involved.
期刊介绍:
Allergology International is the official journal of the Japanese Society of Allergology and publishes original papers dealing with the etiology, diagnosis and treatment of allergic and related diseases. Papers may include the study of methods of controlling allergic reactions, human and animal models of hypersensitivity and other aspects of basic and applied clinical allergy in its broadest sense.
The Journal aims to encourage the international exchange of results and encourages authors from all countries to submit papers in the following three categories: Original Articles, Review Articles, and Letters to the Editor.