{"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":"https://doi.org/10.1016/j.alit.2025.02.001","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":6.2,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefan Zielen, Hartmut Richter, Petra Zieglmayer, Michael Gerstlauer, Josiane Cognet-Sicé, Silvia Scurati, Philippe Devillier
{"title":"Long-term impact of a birch/alder/hazel or birch-only liquid sublingual immunotherapy on birch-family pollen respiratory allergy: A real-world study.","authors":"Stefan Zielen, Hartmut Richter, Petra Zieglmayer, Michael Gerstlauer, Josiane Cognet-Sicé, Silvia Scurati, Philippe Devillier","doi":"10.1016/j.alit.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.alit.2025.02.002","url":null,"abstract":"<p><strong>Background: </strong>Patients with allergic rhinitis (AR) and/or mild or moderate asthma derived from birch-family pollen allergy can be treated with liquid sublingual immunotherapy (SLIT-liquid). This study evaluated the impact of two SLIT extracts on AR and asthma progression or onset in these patients.</p><p><strong>Methods: </strong>This was a sub-analysis of a retrospective, longitudinal comparative cohort study that used a German prescription database. Patients treated with 3-tree (birch/alder/hazel) or birch-only SLIT-liquid and followed up for up to 6 years after treatment were compared with controls dispensed symptomatic medications. Multiple regression analysis compared dispensation data as a proxy for disease status and progression.</p><p><strong>Results: </strong>A total of 493 patients treated with 3-tree SLIT-liquid and 311 treated with birch SLIT-liquid were analysed vs. 44,835 patients included as controls. Overall, 70.5 % of patients presented solely AR, 24.2 % solely asthma, and 5.3 % both diseases. Compared with controls, patients treated with 3-tree SLIT-liquid had reduced risk of AR [odds ratio (OR) = 3.21, 95 % CI 2.54-4.06, p < 0.001], asthma progression (OR = 2.03, 95 % CI 1.43-2.89, p < 0.0001), or asthma onset (OR = 0.592, 95 % CI, 0.408-0.860, p = 0.006). Birch-only SLIT-liquid showed similar effectiveness in reducing AR and asthma medication dispensation but no significant effect in reducing new-onset asthma.</p><p><strong>Conclusions: </strong>This real-world study demonstrated the effectiveness of treatment with 3-tree SLIT-liquid or birch SLIT-liquid in slowing the progression of birch-family pollen allergy. 3-tree SLIT-liquid covering a broader repertoire of epitopes mimicking natural exposure throughout the year may be valuable for patients sensitised to birch and/or alder and/or hazel pollen suffering from overlapping tree-pollen seasons.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mo Xian, Anish R Maskey, Daniel Kopulos, Xiu-Min Li
{"title":"The roles of bitter and sweet taste receptors in food allergy: Where are we now?","authors":"Mo Xian, Anish R Maskey, Daniel Kopulos, Xiu-Min Li","doi":"10.1016/j.alit.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.alit.2025.01.005","url":null,"abstract":"<p><p>Food allergy (FA) is a growing global concern, which contributes significantly to anaphylaxis and severe allergic reactions. Despite advancements in treatments like allergen immunotherapy and biologics, current approaches have notable limitations and there is a pressing need for new therapeutic strategies. Recent research into taste receptors has unveiled their potential role in FA, offering fresh perspectives for understanding and managing this condition. Taste receptors, particularly type 1 taste receptors (TAS1Rs/T1Rs, sweet taste receptors) and type 2 taste receptors (TAS2Rs/T2Rs, bitter taste receptors), are distributed not only in the oral cavity but also in various extra-oral tissues, and their interactions with immune responses are increasingly recognized. This review highlights the connections between taste receptors and FA, exploring how taste receptor mechanisms might contribute to FA pathogenesis and treatment. Taste receptors, especially TAS2Rs, which include multiple subtypes with varying ligand specificities, have been implicated in modulating allergic responses and could serve as targets for novel FA therapies. Additionally, compounds such as bitter agents and sweeteners that interact with taste receptors show promise in influencing FA outcomes. This review emphasizes the need for further research into the mechanisms of taste receptor involvement in FA and suggests that targeting these receptors could provide new avenues for therapeutic intervention in the future.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The relationship of polyunsaturated and monounsaturated fatty acids intake and serum concentrations on inhalant allergen sensitization and allergic rhinitis development.","authors":"Chihiro Nakamura, Atsushi Matsubara, Ayami Nomura, Junko Takahata, Kaori Sawada, Shigeyuki Nakaji","doi":"10.1016/j.alit.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.alit.2024.12.009","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of allergic rhinitis may be attributed to lifestyle changes such as dietary habits. Regarding dietary factors, n-3 and n-6 polyunsaturated fatty acids (PUFAs) are considered to be involved in the pathogenesis. Therefore, we examined whether the intake and serum concentrations of fatty acids affect inhaled allergen sensitization and the development of allergic rhinitis.</p><p><strong>Methods: </strong>In total, 571 participants (20-69 years) from the Iwaki Health Promotion Project, a community-based project in 2022, were surveyed. Based on the results of PUFA intake and serum fatty acid concentrations obtained using a self-administered diet-history questionnaire, we examined whether n-3 or n-6 PUFAs were involved in reducing or increasing the risk of sensitization, respectively, and developing the disease. We also analyzed whether monounsaturated fatty acids-palmitoleic acid and oleic acid-were risk factors for sensitization and development. Univariate dietary intake, serum concentration, and logistic regression analyses were performed to identify the risk factors.</p><p><strong>Results: </strong>Our study revealed that higher serum concentrations of n-3 PUFAs were associated with a decreased risk of developing rhinitis, but had no effect on allergen sensitization in younger age group <50 years. Furthermore, palmitoleic acid had increased sensitization, and oleic acid may also increase the risk of the allergen sensitization.</p><p><strong>Conclusions: </strong>n-3 PUFAs may reduce the risk of developing allergic rhinitis. Notably, palmitoleic acid may be a new risk factor that increases the risk of inhalant allergen sensitization and allergic rhinitis. These findings are significant in understanding the role of dietary factors in allergic rhinitis.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ge Peng, Wanchen Zhao, Alafate Abudouwanli, Quan Sun, Mengyao Yang, Shan Wang, Yi Tan, Arisa Ikeda, Shigaku Ikeda, Hideoki Ogawa, Ko Okumura, François Niyonsaba
{"title":"Improvement of atopic dermatitis-like symptoms in a murine model via the chromogranin A-derived peptide catestatin.","authors":"Ge Peng, Wanchen Zhao, Alafate Abudouwanli, Quan Sun, Mengyao Yang, Shan Wang, Yi Tan, Arisa Ikeda, Shigaku Ikeda, Hideoki Ogawa, Ko Okumura, François Niyonsaba","doi":"10.1016/j.alit.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.alit.2025.01.001","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is characterized by compromised skin barrier and heightened immune responses. The study investigates the therapeutic efficacy of catestatin (CST), a chromogranin A-derived antimicrobial peptide, in mitigating AD-like symptoms.</p><p><strong>Methods: </strong>Utilizing both keratinocyte cultures and a C57BL/6 mouse model, we examined CST's impact on skin barrier proteins, tight junction (TJ) integrity, inflammatory cytokines, and AD-like symptoms.</p><p><strong>Results: </strong>CST administration led to a significant upregulation of skin barrier proteins and improved TJ function, counteracting the negative effects of Th2 cytokines on these parameters. In a 2,4-dinitrochlorobenzene-induced AD mouse model, CST treatment markedly reduced AD-like symptoms, including ear thickness, transepidermal water loss, and scratching behavior, and normalized barrier protein expression and TJ barrier function. Furthermore, CST was found to interact with the Notch1 receptor, activating the Notch1/PKC pathway, which may underlie its skin barrier-enhancing properties.</p><p><strong>Conclusions: </strong>Collectively, these findings suggest CST as a promising therapeutic agent for AD, capable of enhancing skin barrier function, modulating immune responses, and targeting the Notch1/PKC pathway, offering a novel approach to AD treatment focusing on barrier restoration and immune modulation.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Executive summary: Japanese guidelines for atopic dermatitis (ADGL) 2024.","authors":"Hidehisa Saeki, Yukihiro Ohya, Hirokazu Arakawa, Susumu Ichiyama, Toshio Katsunuma, Norito Katoh, Akio Tanaka, Hideaki Tanizaki, Yuichiro Tsunemi, Takeshi Nakahara, Mizuho Nagao, Masami Narita, Michihiro Hide, Takao Fujisawa, Masaki Futamura, Koji Masuda, Tomoyo Matsubara, Hiroyuki Murota, Kiwako Yamamoto-Hanada, Junichi Furuta","doi":"10.1016/j.alit.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.alit.2025.01.003","url":null,"abstract":"<p><p>This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2024. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. A crucial aspect of AD treatment is the prompt induction of remission via the suppression of existing skin inflammation and pruritus. To achieve this, topical anti-inflammatory drugs such as topical corticosteroids, tacrolimus ointment, delgocitinib ointment, and difamilast ointment have been used. However, the following treatments should be considered in addition to topical therapy for patients with refractory moderate-to-severe AD: oral cyclosporine, subcutaneous injections of biologics (dupilumab, nemolizumab, tralokinumab), oral Janus kinase inhibitors (baricitinib, upadacitinib, abrocitinib), and phototherapy. In the revised guidelines, descriptions of five new drugs, namely, difamilast, nemolizumab, tralokinumab, upadacitinib, and abrocitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The gut-organ axis: Clinical aspects and immune mechanisms.","authors":"Naoto Fukasawa, Junya Tsunoda, Shogo Sunaga, Hiroki Kiyohara, Nobuhiro Nakamoto, Toshiaki Teratani, Yohei Mikami, Takanori Kanai","doi":"10.1016/j.alit.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.alit.2025.01.004","url":null,"abstract":"<p><p>The gut-brain axis exemplifies the bidirectional connection between the intestines and the brain, as evidenced by the impact of severe stress on gastrointestinal symptoms including abdominal pain and diarrhea, and conversely, the influence of abdominal discomfort on mood. Clinical observations support the notion of the gut-brain connection, including an increased prevalence of inflammatory bowel disease (IBD) in patients with depression and anxiety, as well as the association of changes in the gut microbiota with neurological disorders such as multiple sclerosis, Parkinson's disease, stroke and Alzheimer's disease. The gut and brain communicate via complex mechanisms involving inflammatory cytokines, immune cells, autonomic nerves, and gut microbiota, which contribute to the pathogenesis in certain gut and brain diseases. Two primary pathways mediate the bidirectional information exchange between the intestinal tract and the brain: signal transduction through bloodstream factors, such as bacterial metabolites and inflammatory cytokines, and neural pathways, such as neurotransmitters and inflammatory cytokines within the autonomic nervous system through the interaction between the nerve cells and beyond. In recent years, the basic mechanisms of the pathophysiology of the gut-brain axis have been gradually elucidated. Beyond the gut-brain interaction, emerging evidence suggests the influence of the gut extends to other organs, such as the liver and lungs, through intricate inter-organ communication pathways. An increasing number of reports on this clinical and basic cross-organ interactions underscore the potential for better understanding and novel therapeutic strategies targeting inter-organs networks. Further clarification of interactions between multiorgans premises transformative insights into cross-organ therapeutic strategies.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Songhui Kim, Cebile Ndwandwe, Hannah Devotta, Lamiah Kareem, Lu Yao, Liam O'Mahony
{"title":"Role of the microbiome in regulation of the immune system.","authors":"Songhui Kim, Cebile Ndwandwe, Hannah Devotta, Lamiah Kareem, Lu Yao, Liam O'Mahony","doi":"10.1016/j.alit.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.alit.2024.12.006","url":null,"abstract":"<p><p>Immune health and metabolic functions are intimately connected via diet and the microbiota. Immune cells are continuously exposed to a wide range of microbes and microbial-derived compounds, with important mucosal and systemic ramifications. Microbial fermentation of dietary components in vivo generates thousands of molecules, some of which are integral components of the molecular circuitry that regulates immune and metabolic functions. These in turn protect against aberrant inflammatory or hyper-reactive processes and promote effector immune responses that quickly eliminate pathogens, such as SARS-CoV-2. Potent tolerance mechanisms should ensure that these immune cells do not over-react to non-pathogenic factors (e.g. food proteins), while maintaining the ability to respond to infectious challenges in a robust, effective and well controlled manner. In this review we examine the factors and mechanisms that shape microbiota composition and interactions with the host immune system, their associations with immune mediated disorders and strategies for intervention.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and safety of systemic targeted therapies for atopic dermatitis in children: A systematic review and meta-analysis.","authors":"Norio Kawamoto, Hiroki Murai, Kazutaka Nogami, Takeshi Yamamoto, Tomonobu Kikkawa, Motoko Yasutomi-Sakai, Kiwako Yamamoto-Hanada, Masaki Futamura, Yukihiro Ohya","doi":"10.1016/j.alit.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.alit.2024.11.007","url":null,"abstract":"<p><strong>Background: </strong>In recent years, several targeted therapeutic options have become available for the management of atopic dermatitis in children. In this systematic review and meta-analysis, we assessed the efficacy and safety of systemic targeted therapies for atopic dermatitis in children.</p><p><strong>Methods: </strong>A systematic review of literature available in CENTRAL, MEDLINE, Embase, and ICHUSHI databases until January 7, 2023, was performed. Randomized controlled trials of systemic targeted therapies (biologics and small molecules) on children aged 18 years or younger with atopic dermatitis were included. The primary outcomes were the eczema area and severity index (EASI) and adverse events. Other efficacy and safety outcomes were also used for meta-analysis and risk of bias analysis.</p><p><strong>Results: </strong>We included 10 studies reported in 11 articles involving three agents (dupilumab, abrocitinib, and upadacitinib) and 1760 children. Systemic targeted therapies significantly improved eczema severity with an EASI-75 response (risk ratio, 2.99; 95 % confidence interval [CI], 2.66-3.37). However, systemic targeted therapies were associated with treatment-emergent adverse events (risk difference, 0.05; 95 % CI, 0.01-0.09), particularly among small molecules in subgroup analysis, while no such trend was observed with biologics. Systemic targeted therapy also significantly improved other efficacy outcomes, and no significant association was found in the other safety outcomes. There was no risk of bias in any of the outcomes.</p><p><strong>Conclusions: </strong>Our findings indicate that systemic targeted therapies are effective and relatively safe for treating atopic dermatitis in children, although small molecules may pose a slightly higher risk of adverse events.</p>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}