Allergology International最新文献

{"title":"Gut microbiota of one-and-a-half-year-old food-allergic and healthy children","authors":"","doi":"10.1016/j.alit.2024.03.004","DOIUrl":"10.1016/j.alit.2024.03.004","url":null,"abstract":"<div><h3>Background</h3><p>Intestinal bacteria may play a role in the development of food allergies. This study aimed to analyze and compare the gut microbiota of food-allergic children with that of healthy children of the same age.</p></div><div><h3>Methods</h3><p>Stool samples were collected from one-and-a-half-year-old food-allergic (FA group, n = 29) and healthy controls (HC group, n = 19). A questionnaire was provided to examine the children's birth, dietary, medical, and social histories. The gut microbiota was profiled by 16S rRNA sequencing. Differences in taxonomic composition were assessed using linear discriminant analysis effect size (LEfSe), and microbial functional profiles were predicted with Tax4Fun2.</p></div><div><h3>Results</h3><p>No significant difference in the alpha diversity index between the two groups; however, a negative correlation was observed between the Shannon diversity index and the relative abundance of <em>Bacteroides</em>. A significant difference was observed in beta diversity (permutational multivariate analysis of variance) in the bacterial composition between the FA and HC groups (<em>P</em> &lt; 0.05). The FA group had a higher abundance of <em>Escherichia</em> and <em>Anaeromassilibacillus</em> and a lower abundance of <em>Bacteroides</em>, <em>Oscillibacter</em>, <em>Ruminococcus, Hungateiclostridium</em> and <em>Anaerotaenia</em> than the HC group (LEfSe: linear discriminant analysis score &gt;2). The FA group showed a predicted increase in the expression levels of genes associated with intestinal pathogenicity compared with that in the HC group.</p></div><div><h3>Conclusions</h3><p>The gut microbiota of food-allergic children has a higher abundance of bacteria involved in intestinal inflammation and a lower abundance of bacteria involved in immune tolerance than that of healthy children. This dysbiosis may also be associated with food allergies.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 4","pages":"Pages 550-555"},"PeriodicalIF":6.2,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S132389302400042X/pdfft?md5=df0126a6bc0acb112048fcdd3d8f1a04&pid=1-s2.0-S132389302400042X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and genetic HLA marker for patients with oxaliplatin-induced adverse drug reactions","authors":"","doi":"10.1016/j.alit.2024.03.003","DOIUrl":"10.1016/j.alit.2024.03.003","url":null,"abstract":"<div><h3>Background</h3><p>Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs.</p></div><div><h3>Methods</h3><p>A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The <em>in vitro</em> basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined.</p></div><div><h3>Results</h3><p>The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the <em>HLA-DRB∗12:01</em> allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; <em>P</em> = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; <em>P</em> = 0.001). The <em>in vitro</em> BAT showed higher activation of CD63⁺ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (<em>P</em> &lt; 0.05). Only four patients (8.5%) with oxaliplatin-induced ADRs were positive for oxaliplatin-specific IgE.</p></div><div><h3>Conclusions</h3><p>This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. <em>HLA-DRB∗12:01</em> is regarded as a genetic marker for oxaliplatin-induced hypersensitivity.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 4","pages":"Pages 580-586"},"PeriodicalIF":6.2,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000418/pdfft?md5=789c711192aac0b4d44c30ba22559230&pid=1-s2.0-S1323893024000418-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophilic mucus diseases","authors":"Misaki Arima ,&nbsp;Keisuke Ito ,&nbsp;Tomoe Abe ,&nbsp;Tsuyoshi Oguma ,&nbsp;Koichiro Asano ,&nbsp;Manali Mukherjee ,&nbsp;Shigeharu Ueki","doi":"10.1016/j.alit.2024.03.002","DOIUrl":"10.1016/j.alit.2024.03.002","url":null,"abstract":"<div><p>Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed countries, eosinophilic inflammation is strongly associated with allergic/sterile inflammation, and constitutes an undesired immune reaction. This situation is in stark contrast to neutrophilic inflammation, which is indispensable for the host defense against bacterial infections. Among eosinophilic inflammatory disorders, massive accumulation of eosinophils within mucus is observed in certain cases, and is often linked to the distinctive clinical finding of mucus with high viscosity. Eosinophilic mucus is found in a variety of diseases, including chronic allergic keratoconjunctivitis, chronic rhinosinusitis encompassing allergic fungal sinusitis, eosinophilic otitis media, eosinophilic sialodochitis, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic plastic bronchitis, and eosinophilic asthma. In these pathological conditions, chronic inflammation and tissue remodeling coupled with irreversible organ damage due to persistent adhesion of toxic substances and luminal obstruction may impose a significant burden on the body. Eosinophils aggregate in the hyperconcentrated mucus together with cell-derived crystals, macromolecules, and polymers, thereby affecting the biophysical properties of the mucus. This review focuses on the clinically significant challenges of mucus and discusses the consequences of activated eosinophils on the mucosal surface that impact mucus and persistent inflammation.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 362-374"},"PeriodicalIF":6.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000406/pdfft?md5=7158278c7912eb805be4dba1fabf6991&pid=1-s2.0-S1323893024000406-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood eosinophil phenotype during treatment with mepolizumab in patients with severe eosinophilic asthma","authors":"Chio Sakai ,&nbsp;Masashi Matsuyama ,&nbsp;Masayuki Nakajima ,&nbsp;Sosuke Matsumura ,&nbsp;Mizu Nonaka ,&nbsp;Naoki Arai ,&nbsp;Kenya Kuramoto ,&nbsp;Kazufumi Yoshida ,&nbsp;Yuko Morishima ,&nbsp;Masafumi Muratani ,&nbsp;Nobuyuki Hizawa","doi":"10.1016/j.alit.2024.03.005","DOIUrl":"10.1016/j.alit.2024.03.005","url":null,"abstract":"","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 473-476"},"PeriodicalIF":6.8,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000431/pdfft?md5=798900522ecda0e1edca43ad512ffce6&pid=1-s2.0-S1323893024000431-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of food protein-induced enterocolitis syndrome (FPIES)","authors":"Masayuki Akashi ,&nbsp;Sachiko Kaburagi ,&nbsp;Naoki Kajita ,&nbsp;Hideaki Morita","doi":"10.1016/j.alit.2024.02.001","DOIUrl":"https://doi.org/10.1016/j.alit.2024.02.001","url":null,"abstract":"<div><p>Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with gastrointestinal symptoms such as vomiting and diarrhea. The development of international consensus guidelines for the diagnosis and management of FPIES in 2017 enabled us to compare patients worldwide, regardless of geographic variation in disease features. As a result, it has become clear that there is heterogeneity among patients with FPIES or that there are cases that partly fit the diagnostic criteria for FPIES but have different characteristics. This review highlights the heterogeneity in FPIES characteristics in terms of trigger foods, the age of onset, differences in geographic regions, and symptoms; it further proposes four disease entities, including acute FPIES in children, acute FPIES in adults, chronic FPIES, and early-onset neonatal FPIES, depending on the age of onset and presumed pathophysiology. The major symptoms at onset and trigger foods differ in acute FPIES in children, acute FPIES in adults, and chronic FPIES, whereas the disease entities may share a similar pathophysiology. Early-onset neonatal FPIES may have a different pathophysiology than acute or chronic FPIES, and may not necessarily fulfil the full diagnostic criteria for acute or chronic FPIES described in the international consensus guidelines. Due to the similarity in symptoms, early-onset neonatal FPIES may sometimes be misdiagnosed as necrotizing enterocolitis. We aim to increase awareness of FPIES among medical staff in pediatrics, neonatology, and internal medicine and promote research, to gain a better understanding of the heterogeneity and pathophysiology of FPIES.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 2","pages":"Pages 196-205"},"PeriodicalIF":6.8,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000145/pdfft?md5=0fa74101d6a99be00ba5aacf69ed0ce5&pid=1-s2.0-S1323893024000145-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140309871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophil-mucus interplay in severe asthma: Implications for treatment with biologicals","authors":"Carmen Venegas Garrido,&nbsp;Manali Mukherjee,&nbsp;Sarah Svenningsen,&nbsp;Parameswaran Nair","doi":"10.1016/j.alit.2024.03.001","DOIUrl":"10.1016/j.alit.2024.03.001","url":null,"abstract":"<div><p>Airway mucus is a hydrogel with unique biophysical properties due to its primary water composition and a small proportion of large anionic glycoproteins or mucins. The predominant mucins in human mucus, MUC5AC and MUC5B, are secreted by specialized cells within the airway epithelium both in normal conditions and in response to various stimuli. Their relative proportions are correlated with specific inflammatory responses and disease mechanisms. The dysregulation of mucin expression is implicated in numerous respiratory diseases, including asthma, COPD, and cystic fibrosis, where the pathogenic role of mucus has been extensively described yet often overlooked. In airway diseases, excessive mucus production or impaired mucus clearance leads to mucus plugging, with secondary airway occlusion that contribute to airflow obstruction, asthma severity and poor control. Eosinophils and Charcot Leyden crystals in sputum contribute to the mucus burden and tenacity. Mucin may also contribute to eosinophil survival. Other mechanisms, including eosinophil-independent IL-13 release, mast-cell activation and non-type-2 (T2) cytokines, are also likely to participate in mucus pathobiology. An accurate assessment of mucus and its clinical and functional consequences require a thorough approach that includes evaluation of cellular predominance in sputum, airway cytokines and other inflammatory markers, mucus characteristics and composition and structural and functional impact measured by advanced lung imaging. This review, illustrated with clinical scenarios, provides an overview of current methods to assess mucus and its relevance to the choice of biologics to treat patients with severe asthma.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 351-361"},"PeriodicalIF":6.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000182/pdfft?md5=d635d13d9bd94db1f60e301b0de24772&pid=1-s2.0-S1323893024000182-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of dupilumab for airway hypersecretion and airway wall thickening in patients with moderate-to-severe asthma: A prospective, observational study","authors":"Tomoko Tajiri ,&nbsp;Motohiko Suzuki ,&nbsp;Hirono Nishiyama ,&nbsp;Yoshiyuki Ozawa ,&nbsp;Ryota Kurokawa ,&nbsp;Norihisa Takeda ,&nbsp;Keima Ito ,&nbsp;Kensuke Fukumitsu ,&nbsp;Yoshihiro Kanemitsu ,&nbsp;Yuta Mori ,&nbsp;Satoshi Fukuda ,&nbsp;Takehiro Uemura ,&nbsp;Hirotsugu Ohkubo ,&nbsp;Masaya Takemura ,&nbsp;Ken Maeno ,&nbsp;Yutaka Ito ,&nbsp;Tetsuya Oguri ,&nbsp;Kenji Izuhara ,&nbsp;Akio Niimi","doi":"10.1016/j.alit.2024.02.002","DOIUrl":"10.1016/j.alit.2024.02.002","url":null,"abstract":"<div><h3>Background</h3><p>Dupilumab has clinical effects in patients with moderate-to-severe asthma. When considering interleukin (IL)-4 and IL-13 signaling, effects of dupilumab on airway mucus hypersecretion and airway remodeling are expected, but they have been reported in only a few short-term studies. Its efficacy for airway hyperresponsiveness (AHR) remains unknown. We comprehensively assessed the efficacy of dupilumab, especially for subjective and objective measures of airway mucus hypersecretion and airway dimensions in moderate-to-severe asthmatic patients.</p></div><div><h3>Methods</h3><p>In 28 adult patients with moderate-to-severe uncontrolled asthma, the comprehensive efficacy of 48-week dupilumab treatment, including the Cough and Sputum Assessment Questionnaire (CASA-Q), radiological mucus scores and airway dimensions on computed tomography (CT), was assessed prospectively. Treatment responsiveness to dupilumab was analyzed.</p></div><div><h3>Results</h3><p>With 48-week dupilumab treatment, all four cough and sputum domain scores of CASA-Q improved significantly. Radiological mucus scores and airway wall thickening on CT were significantly decreased. The decreases in mucus scores were significantly associated with improvements in Asthma Control Questionnaire scores, Asthma Quality of Life Questionnaire (AQLQ) overall scores, airway obstruction, and airway type 2 inflammation. When defined by &gt; 0.5 improvement in AQLQ overall scores, 18 patients (64%) were identified as responders.</p></div><div><h3>Conclusions</h3><p>Dupilumab reversed subjective and objective measures of airway mucus hypersecretion and some aspects of airway remodeling in patients with moderate-to-severe uncontrolled asthma.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 406-415"},"PeriodicalIF":6.8,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000169/pdfft?md5=998de0273c82bd12812db9d9bb47bbfa&pid=1-s2.0-S1323893024000169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-IgE-mediated food allergy: Where are we now?","authors":"Kenji Matsumoto (Associate Editor, Allergology International)","doi":"10.1016/j.alit.2024.02.003","DOIUrl":"10.1016/j.alit.2024.02.003","url":null,"abstract":"","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 2","pages":"Page 187"},"PeriodicalIF":6.8,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000170/pdfft?md5=3a1294da902e541d78e89c0bc2115739&pid=1-s2.0-S1323893024000170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of fractional exhaled nitric oxide with airway dimension and mucus plugs on ultra-high-resolution computed tomography in former smokers and nonsmokers with asthma","authors":"Yusuke Hayashi ,&nbsp;Naoya Tanabe ,&nbsp;Hisako Matsumoto ,&nbsp;Kaoruko Shimizu ,&nbsp;Ryo Sakamoto ,&nbsp;Tsuyoshi Oguma ,&nbsp;Hironobu Sunadome ,&nbsp;Atsuyasu Sato ,&nbsp;Susumu Sato ,&nbsp;Toyohiro Hirai","doi":"10.1016/j.alit.2024.01.013","DOIUrl":"10.1016/j.alit.2024.01.013","url":null,"abstract":"<div><h3>Background</h3><p>Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways &gt;1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma.</p></div><div><h3>Methods</h3><p>The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored.</p></div><div><h3>Results</h3><p>Ninety-seven patients with asthma (including 59 former smokers) were classified into low (&lt;20 ppb), middle (20–35 ppb), and high (&gt;35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence.</p></div><div><h3>Conclusions</h3><p>Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 3","pages":"Pages 397-405"},"PeriodicalIF":6.8,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893024000157/pdfft?md5=6336b96d162de606b9647933894c8103&pid=1-s2.0-S1323893024000157-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical application of activator protein-1 inhibitor T-5224 suppresses inflammation and improves skin barrier function in a murine atopic dermatitis-like dermatitis","authors":"Minori Sasakura ,&nbsp;Hitoshi Urakami ,&nbsp;Kota Tachibana ,&nbsp;Kenta Ikeda ,&nbsp;Ken-ichi Hasui ,&nbsp;Yoshihiro Matsuda ,&nbsp;Ko Sunagawa ,&nbsp;Daisuke Ennishi ,&nbsp;Shuta Tomida ,&nbsp;Shin Morizane","doi":"10.1016/j.alit.2023.12.006","DOIUrl":"10.1016/j.alit.2023.12.006","url":null,"abstract":"<div><h3>Background</h3><p>Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders.</p></div><div><h3>Methods</h3><p>Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the <em>in vivo</em> study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the <em>in vitro</em> study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines.</p></div><div><h3>Results</h3><p>AP-1/c-Jun was phosphorylated at skin lesions in AD patients. <em>In vivo</em>, topical T-5224 application inhibited ear swelling (P &lt; 0.001), restored <em>filaggrin</em> (<em>Flg</em>) expression (P &lt; 0.01), and generally suppressed immune-related pathways. T-5224 significantly suppressed <em>Il17a</em> and <em>l17f</em> expression, whereas baricitinib did not. Baricitinib suppressed <em>Il4, Il19, Il33</em> and <em>Ifnb</em> expression, whereas T-5224 did not. <em>Il1a, Il1b, Il23a, Ifna, S100a8,</em> and <em>S100a9</em> expression was cooperatively downregulated following the combined use of T-5224 and baricitinib. <em>In vitro,</em> T-5224 restored the expression of <em>FLG</em> and <em>loricrin (LOR)</em> (P &lt; 0.05) and suppressed <em>IL33</em> expression (P &lt; 0.05) without affecting cell viability and cytotoxicity.</p></div><div><h3>Conclusions</h3><p>Topical T-5224 ameliorates clinical manifestations of AD-like dermatitis in mice. The effect of this inhibitor is amplified via combined use with JAK inhibitors.</p></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"73 2","pages":"Pages 323-331"},"PeriodicalIF":6.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1323893023001417/pdfft?md5=0807f48bc05fab1f1d3ae6c04dce9c29&pid=1-s2.0-S1323893023001417-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139730758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}