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Uncovering new players in IL-5 signaling: Mast cells, mast cell progenitors, and beyond
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2025.01.037
Tanya M. Laidlaw MD
{"title":"Uncovering new players in IL-5 signaling: Mast cells, mast cell progenitors, and beyond","authors":"Tanya M. Laidlaw MD","doi":"10.1016/j.jaci.2025.01.037","DOIUrl":"10.1016/j.jaci.2025.01.037","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1205-1207"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mesenchymal stem cell-derived small extracellular vesicles restored nasal barrier function in allergic rhinitis via miR-143–GSK3B in human nasal epithelial cells 间充质干细胞衍生的细胞外小泡通过人鼻上皮细胞中的miR-143-GSK3β恢复过敏性鼻炎的鼻屏障功能
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2024.10.034
Meiqian Xu PhD , Mei Ren MD , Xinyin Zhang BA , Wenxu Peng BA , Hao Li PhD , Wenjing Liao PhD , Jianlei Xie PhD , Xiaowen Zhang PhD
{"title":"Mesenchymal stem cell-derived small extracellular vesicles restored nasal barrier function in allergic rhinitis via miR-143–GSK3B in human nasal epithelial cells","authors":"Meiqian Xu PhD ,&nbsp;Mei Ren MD ,&nbsp;Xinyin Zhang BA ,&nbsp;Wenxu Peng BA ,&nbsp;Hao Li PhD ,&nbsp;Wenjing Liao PhD ,&nbsp;Jianlei Xie PhD ,&nbsp;Xiaowen Zhang PhD","doi":"10.1016/j.jaci.2024.10.034","DOIUrl":"10.1016/j.jaci.2024.10.034","url":null,"abstract":"<div><h3>Background</h3><div>The nasal epithelial barrier is the first line of defense against the deep entry of pathogens or aeroallergens and is more critical in allergic rhinitis (AR). Restoring epithelial barrier dysfunction might be a promising strategy for AR. Recent studies reported that mesenchymal stem cell–derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and promote tissue regeneration. However, their effect on nasal epithelial cells remains unknown.</div></div><div><h3>Objectives</h3><div>This study sought to describe the therapeutic effect of MSC-sEV on AR, particularly focusing their effect on nasal epithelial cells and underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>We utilized an ovalbumin-induced mouse model to study AR. Both primary and immortalized human nasal epithelial cells (HNEpC) were used to further validate the therapeutic effects of MSC-sEV on epithelial cell function. Then we constructed microRNA (miR)-143 overexpressing and low-expressing HNEpC and MSC-sEV to elucidate molecular mechanisms. Transcriptome analysis was performed to identify the downstream pathways involved.</div></div><div><h3>Results</h3><div>MSC-sEV successfully maintained nasal barrier integrity in AR mouse model. The MSC-sEV therapeutic effect on the nasal barrier was substantiated in HNEpC. Mechanistically, miR-143 was a candidate mediator of the above effects. Subsequently, transfecting HNEpC with miR-143 partially mimicked the restoring effect of MSC-sEV. MSC-sEV overexpressing miR-143 exerted more therapeutic effects on tight junctions and barrier integrity. Moreover, miR-143 regulated the glycogen synthase kinase-3β (GSK3B) pathway.</div></div><div><h3>Conclusions</h3><div>Our results indicated that MSC-sEV mitigated AR and restored nasal epithelial barrier dysfunction through the miR-143–GSK3B axis, which suggested that MSC-sEV have the remarkable ability to treat AR.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1236-1249.e5"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DOCK8 at the crossroads of immunodeficiency and hyperinflammation DOCK8在免疫缺陷和高炎症的十字路口。
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2024.12.1072
Casey A. Rimland MD, PhD , Michael T. Lam MD, PhD , Pui Y. Lee MD, PhD
{"title":"DOCK8 at the crossroads of immunodeficiency and hyperinflammation","authors":"Casey A. Rimland MD, PhD ,&nbsp;Michael T. Lam MD, PhD ,&nbsp;Pui Y. Lee MD, PhD","doi":"10.1016/j.jaci.2024.12.1072","DOIUrl":"10.1016/j.jaci.2024.12.1072","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1199-1201"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The relationship between the early-life gastrointestinal microbiome and childhood nocturnal cough 早期胃肠道微生物群与儿童夜间咳嗽的关系。
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2025.01.006
Amy A. Eapen MD, MS , Tengfei Ma PhD , Alexandra R. Sitarik MS , Ze Meng MS , Dennis R. Ownby MD , Andrea E. Cassidy-Bushrow PhD , Ganesa Wegeinka PhD , Edward M. Zoratti MD , Susan V. Lynch PhD , Christine C. Johnson PhD , Albert M. Levin PhD
{"title":"The relationship between the early-life gastrointestinal microbiome and childhood nocturnal cough","authors":"Amy A. Eapen MD, MS ,&nbsp;Tengfei Ma PhD ,&nbsp;Alexandra R. Sitarik MS ,&nbsp;Ze Meng MS ,&nbsp;Dennis R. Ownby MD ,&nbsp;Andrea E. Cassidy-Bushrow PhD ,&nbsp;Ganesa Wegeinka PhD ,&nbsp;Edward M. Zoratti MD ,&nbsp;Susan V. Lynch PhD ,&nbsp;Christine C. Johnson PhD ,&nbsp;Albert M. Levin PhD","doi":"10.1016/j.jaci.2025.01.006","DOIUrl":"10.1016/j.jaci.2025.01.006","url":null,"abstract":"<div><h3>Background</h3><div>Nocturnal cough affects approximately 1 in 3 children, can negatively affect child health, and is often attributable to asthma. The association of the gut microbiome with nocturnal cough has not been investigated.</div></div><div><h3>Objective</h3><div>We investigated the association between early-life gut microbiome composition and nocturnal cough overall and in the context of asthma.</div></div><div><h3>Methods</h3><div>Gut microbiota 1-month (neonate) and 6-month (infant) specimens from 512 children in the Wayne County, Health, Environment, Allergy, and Asthma Longitudinal Study were profiled using 16S ribosomal RNA V4 sequencing. Nocturnal cough (parental report) and asthma (parent-reported doctor’s diagnosis) were assessed at age 4 years. Microbiome regression-based kernel association tests (MiRKAT) were used to assess the relationship between gut microbiota composition and nocturnal cough overall and in the context of asthma. Operational taxonomic unit (OTU) associations were conducted using negative binomial regression, adjusting for multiple comparisons using the false discovery rate.</div></div><div><h3>Results</h3><div>Stool microbial composition differences during infancy were associated with nocturnal cough (weighted UniFrac <em>P</em> = .045); 78 OTUs were significantly associated with nocturnal cough overall (false discovery rate &lt; 0.05); and 110 OTUs were significantly associated with nocturnal cough and differed by asthma status (interaction false discovery rate &lt; 0.05), with a predominance of Lachnospiraceae genera <em>Blautia</em> and <em>Dorea.</em> Thirty-two OTU were identified as having both overall effects and differences by asthma status. Among OTUs with significant nocturnal cough-by-asthma interactions, 84 retained significance in children with asthma, with 45 exclusive to those with asthma (predominance of Bacteroidaceae genus <em>Bacteroides</em> and Lachnospiraceae genus <em>Dorea</em>).</div></div><div><h3>Conclusion</h3><div>Infantile gut microbiome development is associated with nocturnal cough and differed by asthma status by age 4 years. Further studies are needed to determine if the gut microbiome may provide additional information for the early identification of children at risk for nocturnal cough, with and without asthma.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1386-1391"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of mitochondrial DNA copy number in asthma: Agent or bystander?
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2025.01.023
Anurag Agrawal MBBS, PhD , Ira Agrawal , George Davey Smith MD, DSc, MSc
{"title":"The role of mitochondrial DNA copy number in asthma: Agent or bystander?","authors":"Anurag Agrawal MBBS, PhD ,&nbsp;Ira Agrawal ,&nbsp;George Davey Smith MD, DSc, MSc","doi":"10.1016/j.jaci.2025.01.023","DOIUrl":"10.1016/j.jaci.2025.01.023","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1202-1204"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is there a role for vitamin supplementation in pollutant-related childhood asthma?
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2025.01.012
Allen Joe MD , Yueh-Ying Han PhD , Franziska J. Rosser MD, MPH , Augusto A. Litonjua MD, MPH , Juan C. Celedón MD, DrPH, FAAAAI
{"title":"Is there a role for vitamin supplementation in pollutant-related childhood asthma?","authors":"Allen Joe MD ,&nbsp;Yueh-Ying Han PhD ,&nbsp;Franziska J. Rosser MD, MPH ,&nbsp;Augusto A. Litonjua MD, MPH ,&nbsp;Juan C. Celedón MD, DrPH, FAAAAI","doi":"10.1016/j.jaci.2025.01.012","DOIUrl":"10.1016/j.jaci.2025.01.012","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1196-1198"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations 线粒体 DNA 拷贝数变异与哮喘风险、严重程度和恶化的关系。
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2024.08.022
Weiling Xu MD , Yun Soo Hong MD, PhD , Bo Hu PhD , Suzy A.A. Comhair PhD , Allison J. Janocha BS , Joe G. Zein MD, PhD , Ruoying Chen PhD , Deborah A. Meyers PhD , David T. Mauger PhD , Victor E. Ortega MD, PhD , Eugene R. Bleecker MD , Mario Castro MD , Loren C. Denlinger MD, PhD , John V. Fahy MD , Elliot Israel MD , Bruce D. Levy MD , Nizar N. Jarjour MD , Wendy C. Moore MD , Sally E. Wenzel MD , Benjamin Gaston MD , Serpil C. Erzurum MD
{"title":"Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations","authors":"Weiling Xu MD ,&nbsp;Yun Soo Hong MD, PhD ,&nbsp;Bo Hu PhD ,&nbsp;Suzy A.A. Comhair PhD ,&nbsp;Allison J. Janocha BS ,&nbsp;Joe G. Zein MD, PhD ,&nbsp;Ruoying Chen PhD ,&nbsp;Deborah A. Meyers PhD ,&nbsp;David T. Mauger PhD ,&nbsp;Victor E. Ortega MD, PhD ,&nbsp;Eugene R. Bleecker MD ,&nbsp;Mario Castro MD ,&nbsp;Loren C. Denlinger MD, PhD ,&nbsp;John V. Fahy MD ,&nbsp;Elliot Israel MD ,&nbsp;Bruce D. Levy MD ,&nbsp;Nizar N. Jarjour MD ,&nbsp;Wendy C. Moore MD ,&nbsp;Sally E. Wenzel MD ,&nbsp;Benjamin Gaston MD ,&nbsp;Serpil C. Erzurum MD","doi":"10.1016/j.jaci.2024.08.022","DOIUrl":"10.1016/j.jaci.2024.08.022","url":null,"abstract":"<div><h3>Background</h3><div>Asthma pathophysiology is associated with mitochondrial dysfunction. Mitochondrial DNA copy number (mtDNA-CN) has been used as a proxy of mitochondrial function, with lower levels indicating mitochondrial dysfunction in population studies of cardiovascular diseases and cancers.</div></div><div><h3>Objectives</h3><div>We investigated whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations.</div></div><div><h3>Methods</h3><div>mtDNA-CN is evaluated in blood from 2 cohorts: UK Biobank (UKB) (asthma, n = 39,147; no asthma, n = 302,302) and Severe Asthma Research Program (SARP) (asthma, n = 1283; nonsevere asthma, n = 703).</div></div><div><h3>Results</h3><div>Individuals with asthma have lower mtDNA-CN compared to individuals without asthma in UKB (beta, −0.006 [95% confidence interval, −0.008 to −0.003], <em>P</em> = 6.23 × 10<sup>−6</sup>). Lower mtDNA-CN is associated with asthma prevalence, but not severity in UKB or SARP. mtDNA-CN declines with age but is lower in individuals with asthma than in individuals without asthma at all ages. In a 1-year longitudinal study in SARP, mtDNA-CN was associated with risk of exacerbation; those with highest mtDNA-CN had the lowest risk of exacerbation (odds ratio 0.333 [95% confidence interval, 0.173 to 0.542], <em>P</em> = .001). Biomarkers of inflammation and oxidative stress are higher in individuals with asthma than without asthma, but the lower mtDNA-CN in asthma is independent of general inflammation or oxidative stress. Mendelian randomization studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN.</div></div><div><h3>Conclusion</h3><div>mtDNA-CN is lower in asthma than in no asthma and is associated with exacerbations. Low mtDNA-CN in asthma is not mediated through inflammation but is associated with a genetic predisposition to asthma.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1224-1235"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting of the IL-5 pathway in severe asthma reduces mast cell progenitors 针对严重哮喘的 IL-5 通路可减少肥大细胞祖细胞。
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2024.10.025
P. Abigail Alvarado-Vazquez PhD , Erika Mendez-Enriquez PhD , Maya Salomonsson PhD , Peter Kopac MD, PhD , Ana Koren PhD , Urska Bidovec-Stojkovic PhD , Sabina Škrgat MD, PhD , Oscar E. Simonson MD, PhD , Valentyna Yasinska MD, PhD , Sven-Erik Dahlén MD, PhD , Gunnar Pejler PhD , Christer Janson MD, PhD , Peter Korosec PhD , Andrei Malinovschi MD, PhD , Jenny Hallgren PhD
{"title":"Targeting of the IL-5 pathway in severe asthma reduces mast cell progenitors","authors":"P. Abigail Alvarado-Vazquez PhD ,&nbsp;Erika Mendez-Enriquez PhD ,&nbsp;Maya Salomonsson PhD ,&nbsp;Peter Kopac MD, PhD ,&nbsp;Ana Koren PhD ,&nbsp;Urska Bidovec-Stojkovic PhD ,&nbsp;Sabina Škrgat MD, PhD ,&nbsp;Oscar E. Simonson MD, PhD ,&nbsp;Valentyna Yasinska MD, PhD ,&nbsp;Sven-Erik Dahlén MD, PhD ,&nbsp;Gunnar Pejler PhD ,&nbsp;Christer Janson MD, PhD ,&nbsp;Peter Korosec PhD ,&nbsp;Andrei Malinovschi MD, PhD ,&nbsp;Jenny Hallgren PhD","doi":"10.1016/j.jaci.2024.10.025","DOIUrl":"10.1016/j.jaci.2024.10.025","url":null,"abstract":"<div><h3>Background</h3><div>Therapies targeting IL-5 or its receptor (IL-5Rα) are currently used to treat patients with severe eosinophilic asthma.</div></div><div><h3>Objective</h3><div>We sought to investigate the impact of anti–IL-5 and anti–IL-5Rα biological therapies on mast cells (MCs) and their progenitors.</div></div><div><h3>Methods</h3><div>Surface IL-5Rα expression was investigated on MCs and their progenitors in mouse lungs and bone marrow and in human lungs and blood. Isolated human MC progenitors cultured in the presence or absence of IL-5 were analyzed <em>in vitro</em>. Circulating MC progenitors were quantified in patients with severe asthma before and after anti–IL-5 (mepolizumab) or anti–IL-5Rα (benralizumab) therapy. Gene expression analysis of MC progenitors was performed before and after anti–IL-5Rα therapy.</div></div><div><h3>Results</h3><div>Approximately 50% of the human primary lung MCs and 30% of the human MC progenitors from individuals with allergic asthma expressed IL-5Rα. In patients with mild to moderate allergic asthma and mice with acute allergic airway inflammation, the fraction of IL-5Rα<sup>+</sup> MC progenitors was elevated. In addition, IL-5 promoted the proliferation and/or survival of isolated human MC progenitors. Furthermore, patients with severe asthma from 2 independent cohorts demonstrated a reduction in blood MC progenitors after anti–IL-5 or anti–IL-5Rα treatment. This was associated with improved asthma control as well as a decline in both blood eosinophils and T<sub>H</sub>2 cells. Finally, the blood MC progenitors remaining after anti–IL-5Rα (benralizumab) treatment exhibited a downregulated expression of genes involved in growth and proliferation.</div></div><div><h3>Conclusions</h3><div>This study introduces the possibility that the clinical effects of targeting IL-5/IL-5Rα in severe asthma may also involve reduction of MC populations.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1310-1320"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Update on mast cell biology 肥大细胞生物学最新进展。
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2024.12.1092
Hadas Tamar Pahima PhD , Daniel F. Dwyer PhD
{"title":"Update on mast cell biology","authors":"Hadas Tamar Pahima PhD ,&nbsp;Daniel F. Dwyer PhD","doi":"10.1016/j.jaci.2024.12.1092","DOIUrl":"10.1016/j.jaci.2024.12.1092","url":null,"abstract":"<div><div>Mast cells (MCs) are heterogeneous tissue-resident effector cells that are thought to play central roles in allergic inflammatory disease, yet the degree of heterogeneity and nature of these roles has remained elusive. In recent years, advances in tissue culture systems, preclinical mouse models, and the continued spread of single-cell RNA sequencing have greatly advanced our understanding of MC phenotypes in health and disease. These approaches have identified novel interactions of MC subsets with immune cells, neurons, and tissue structural cells, changing our understanding of how MCs both drive and help resolve tissue inflammation, reshape tissue microenvironments, and influence host behavior. This review addresses key studies from 2022 to 2024 that have advanced our understanding of MC biology in mice and humans.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1115-1123"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Eosinophilic esophagitis drives tissue fibroblast regenerative programs toward pathologic dysfunction 嗜酸性食管炎驱使组织成纤维细胞再生程序走向病理功能障碍。
IF 11.4 1区 医学
Journal of Allergy and Clinical Immunology Pub Date : 2025-04-01 DOI: 10.1016/j.jaci.2024.11.028
Medet Jumabay MD, PhD , Edsel M. Abud MD, PhD , Kevin Okamoto BS , Paramita Dutta MSc , Austin W.T. Chiang PhD , Haining Li MS , Mario C. Manresa PhD , Yanfang P. Zhu PhD , Dana Frederick MS , Richard Kurten PhD , Ben Croker PhD , Nathan E. Lewis PhD , Joshua L. Kennedy MD , Ranjan Dohil MD , Michael Croft PhD , Ferhat Ay PhD , Joshua B. Wechsler MD, MS , Seema S. Aceves MD, PhD
{"title":"Eosinophilic esophagitis drives tissue fibroblast regenerative programs toward pathologic dysfunction","authors":"Medet Jumabay MD, PhD ,&nbsp;Edsel M. Abud MD, PhD ,&nbsp;Kevin Okamoto BS ,&nbsp;Paramita Dutta MSc ,&nbsp;Austin W.T. Chiang PhD ,&nbsp;Haining Li MS ,&nbsp;Mario C. Manresa PhD ,&nbsp;Yanfang P. Zhu PhD ,&nbsp;Dana Frederick MS ,&nbsp;Richard Kurten PhD ,&nbsp;Ben Croker PhD ,&nbsp;Nathan E. Lewis PhD ,&nbsp;Joshua L. Kennedy MD ,&nbsp;Ranjan Dohil MD ,&nbsp;Michael Croft PhD ,&nbsp;Ferhat Ay PhD ,&nbsp;Joshua B. Wechsler MD, MS ,&nbsp;Seema S. Aceves MD, PhD","doi":"10.1016/j.jaci.2024.11.028","DOIUrl":"10.1016/j.jaci.2024.11.028","url":null,"abstract":"<div><h3>Background</h3><div>Pathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE-associated tissue remodeling causes clinical dysphagia, food impactions, esophageal rigidity, and strictures, molecular mechanisms driving these complications remain under investigation.</div></div><div><h3>Objective</h3><div>We hypothesized that chronic EoE inflammation induces pathogenic fibroblasts with dysfunctional tissue regeneration and motility.</div></div><div><h3>Methods</h3><div>We used single-cell RNA sequencing, fluorescence-activated cell sorting analysis, and fibroblast differentiation and migration assays to decipher the induced and retained pathogenic dysfunctions in EoE versus healthy esophageal fibroblasts.</div></div><div><h3>Results</h3><div>Differentiation assays demonstrated that active EoE fibroblasts retain regenerative programs for rigid cells such as chondrocytes (<em>P</em> &lt; .05) but lose healthy fibroblast capacity for soft cells such as adipocytes (<em>P</em> &lt; .01), which was reflected in biopsy sample immunostaining (<em>P</em> &lt; .01). EoE, but not healthy, fibroblasts show proinflammatory and prorigidity transcriptional programs on single-cell RNA sequencing. <em>In vivo,</em> regenerative fibroblasts reside in perivascular regions and near the epithelial junction, and during EoE, they have significantly increased migration (<em>P</em> &lt; .01). Flow analysis and functional assays demonstrated that regenerative EoE fibroblasts have decreased surface CD73 expression and activity (both <em>P</em> &lt; .05) compared to healthy controls, indicating aberrant adenosine triphosphate handling. EoE fibroblast dysfunctions were induced in healthy fibroblasts by reducing CD73 activity and rescued in EoE using adenosine repletion.</div></div><div><h3>Conclusion</h3><div>A normalization of perturbed extracellular adenosine triphosphate handling and CD73 could improve pathogenic fibroblast dysfunction and tissue regeneration in type 2 inflammatory diseases.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1333-1345"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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