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...
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Elsevier
2025-04-01
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| Series: | Allergology International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893025000115 |
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| author | Masato Tamari Aaron M. Ver Heul |
| author_facet | Masato Tamari Aaron M. Ver Heul |
| author_sort | Masato Tamari |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-01178fc7a9534c3eac39529aeb048ea8 |
| institution | Kabale University |
| issn | 1323-8930 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
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| series | Allergology International |
| spelling | doaj-art-01178fc7a9534c3eac39529aeb048ea82025-08-20T03:42:19ZengElsevierAllergology International1323-89302025-04-0174217718610.1016/j.alit.2025.02.001Neuroimmune mechanisms of type 2 inflammation in the skin and lungMasato Tamari0Aaron M. Ver Heul1Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; Corresponding author. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Setagayaku, Tokyo, 157-8535, Japan.Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, USA; Corresponding author. Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63130, USA.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.http://www.sciencedirect.com/science/article/pii/S1323893025000115CytokineNeuroimmune interactionNeuropeptideNeurotransmitterPeripheral nervous system |
| spellingShingle | Masato Tamari Aaron M. Ver Heul Neuroimmune mechanisms of type 2 inflammation in the skin and lung Allergology International Cytokine Neuroimmune interaction Neuropeptide Neurotransmitter Peripheral nervous system |
| title | Neuroimmune mechanisms of type 2 inflammation in the skin and lung |
| title_full | Neuroimmune mechanisms of type 2 inflammation in the skin and lung |
| title_fullStr | Neuroimmune mechanisms of type 2 inflammation in the skin and lung |
| title_full_unstemmed | Neuroimmune mechanisms of type 2 inflammation in the skin and lung |
| title_short | Neuroimmune mechanisms of type 2 inflammation in the skin and lung |
| title_sort | neuroimmune mechanisms of type 2 inflammation in the skin and lung |
| topic | Cytokine Neuroimmune interaction Neuropeptide Neurotransmitter Peripheral nervous system |
| url | http://www.sciencedirect.com/science/article/pii/S1323893025000115 |
| work_keys_str_mv | AT masatotamari neuroimmunemechanismsoftype2inflammationintheskinandlung AT aaronmverheul neuroimmunemechanismsoftype2inflammationintheskinandlung |