Journal of Allergy and Clinical Immunology最新文献

{"title":"Transcriptomic profiling of vitiligo patients shows polar immune dysregulation in involved and uninvolved skin","authors":"Patrick M. Brunner MD, MSc ,&nbsp;Eden David MD ,&nbsp;Ester Del Duca MD ,&nbsp;Meredith Manson BA ,&nbsp;Agata Kurowski PhD ,&nbsp;Malini P. Naidu BA ,&nbsp;Lauren R. Port BA ,&nbsp;Jesus Gay-Mimbrera PhD ,&nbsp;Pedro J. Gómez-Arias MD ,&nbsp;Natalia Alkon PhD ,&nbsp;Jessica Beaziz-Tordjman MD ,&nbsp;Yeriel Estrada BS ,&nbsp;Yael Renert-Yuval MD, MSc ,&nbsp;Juan Ruano MD, PhD ,&nbsp;Emma Guttman-Yassky MD, PhD","doi":"10.1016/j.jaci.2025.06.002","DOIUrl":"10.1016/j.jaci.2025.06.002","url":null,"abstract":"<div><h3>Background</h3><div><span><span><span>Vitiligo is a chronic autoimmune skin depigmenting disorder, with a major impact on </span>quality of life. Therapeutic options are still limited, with only one topical </span>JAK inhibitor being approved by the US Food and Drug Administration. Although vitiligo is primarily regarded as a T</span>_H1/interferon-driven disease, emerging evidence suggests the involvement of additional immune axes, but their relevance to disease pathogenesis remains unclear.</div></div><div><h3>Objective</h3><div>We sought to obtain a global cutaneous transcriptomic profile of lesional and nonlesional vitiligo.</div></div><div><h3>Methods</h3><div><span>We performed bulk RNA sequencing<span> combined with real-time PCR and immunohistochemistry of </span></span>skin biopsy samples from 15 lesional and nonlesional vitiligo samples and compared them to 14 matched healthy controls. Results were corroborated by single-cell RNA sequencing.</div></div><div><h3>Results</h3><div>Robust inflammatory dysregulation was captured not only in lesional but also nonlesional vitiligo skin relative to healthy controls. Lesional samples demonstrated upregulation of T_H1 <em>(OASL, CXCL9, CXCL10),</em> T_H2 <em>(IL4, IL4R, CCL13, CCL17, CCL22, CCL26),</em> and T_H17/22 <em>(IL20, S100A7, S100A8, S100A9, PI3)</em> related markers. Similarly, nonlesional samples demonstrated activation of T_H1 <em>(CXCL9, OASL),</em> T_H2 <em>(IL4R, IL10, CCL13, CCL17, CCL22),</em> and T_H17/22 <em>(PI3, DEFB4A)</em><span> associated markers. Clinical severity scores (Vitiligo Area Scoring Index and/or Vitiligo Disease Activity Index) significantly and positively correlated with multiple inflammatory mediators (ie, </span><em>CXCL14, IL25, IL17RC</em>) in lesional and/or nonlesional vitiligo skin. On a single-cell level, <em>IL13</em> and <em>IFNG</em><span> expression were primarily found in nonlesional helper T cells and in lesional proliferating T cells, respectively.</span></div></div><div><h3>Conclusions</h3><div><span>Our findings show that immune dysregulation in vitiligo involves immune axes beyond T</span>_H1/Tc1, with particular upregulation of type 2 markers already observed in nonlesional skin, suggesting a role during early lesion formation.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 993-1007"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293773","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}

{"title":"Inhibition of lysosomal degradation increases expression of mutant ADA2 in DADA2 monocytes","authors":"Lisa Ehlers MD, PhD ,&nbsp;Marjon Wouters MS ,&nbsp;Bethany Pillay PhD ,&nbsp;Selket Delafontaine MD, PhD ,&nbsp;Mariia Dzhus MD ,&nbsp;Marco Baggio PhD ,&nbsp;Tim Niehues MD ,&nbsp;Gregor Dückers MD ,&nbsp;Lieve Sevenants MD, PhD ,&nbsp;Kristina Casteels MD, PhD ,&nbsp;Lien De Somer MD, PhD ,&nbsp;Rik Schrijvers MD, PhD ,&nbsp;Steven Vanderschueren MD, PhD ,&nbsp;Maarten Jacquemyn MS ,&nbsp;Dirk Daelemans PhD ,&nbsp;Anneleen Hombrouck PhD ,&nbsp;Eugene P. Chambers MD ,&nbsp;Thomas Tousseyn MD, PhD ,&nbsp;Giorgia Bucciol MD, PhD ,&nbsp;Patrizia Agostinis PhD ,&nbsp;Isabelle Meyts PhD","doi":"10.1016/j.jaci.2025.06.009","DOIUrl":"10.1016/j.jaci.2025.06.009","url":null,"abstract":"<div><h3>Background</h3><div>Deficiency of adenosine deaminase 2 (DADA2) is an inborn error of immunity causing vasculitis and bone marrow failure. Bone marrow failure is mostly unresponsive to TNF-α inhibitors. The limited understanding of the pathomechanisms driving the disease impedes the development of new treatment options. Unlike cellular model systems expressing pathogenic <em>ADA2</em> variants, primary monocytes from patients with DADA2 lack ADA2 protein expression.</div></div><div><h3>Objectives</h3><div>This study aimed to analyze the role of protein degradation in the pathogenesis of DADA2 and the therapeutic potential of the lysosomotropic drug hydroxychloroquine in the treatment of patients with DADA2.</div></div><div><h3>Methods</h3><div>ADA2 protein expression in CD14⁺ monocytes from healthy controls (n = 8) and patients with DADA2 (n = 11) was determined by Western blot after inhibition of lysosomal and proteasomal degradation, as well as after hydroxychloroquine treatment <em>in vivo</em> in 1 patient with DADA2. Lipidation of microtubule associated protein 1 light chain 3 beta (LC3B) was analyzed as a measure of autophagic activity. Clinical and laboratory data were recorded in cytopenic patients with DADA2 treated with hydroxychloroquine, 200 mg per day.</div></div><div><h3>Results</h3><div>We demonstrated that inhibition of lysosomal degradation restores ADA2 protein expression in DADA2 monocytes <em>in vitro</em>. DADA2 monocytes exhibited increased autophagic activity. We observed clinical improvement in 2 cytopenic patients with DADA2 who were treated with hydroxychloroquine, and we showed a concomitant increase in ADA2 protein levels in monocytes from one of these patients <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>We identified lysosomal protein degradation of ADA2 as a pathomechanism of DADA2 and introduced hydroxychloroquine as a potential treatment option in patients with DADA2 with refractory cytopenia.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 1111-1119"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368867","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}

{"title":"Human airway epithelial B-cell activating factor is reduced in early life but is virally induced via JAK/STAT","authors":"Elizabeth Chorvinsky MS ,&nbsp;Surajit Bhattacharya PhD ,&nbsp;Kyle Salka MS ,&nbsp;Bethlehem S. Bera MS ,&nbsp;Allison Welham BS ,&nbsp;Ethan Mondell BS ,&nbsp;Geovanny F. Perez MD, MS ,&nbsp;Dinesh Pillai MD, MBA ,&nbsp;Jyoti Jaiswal PhD ,&nbsp;Gustavo Nino MD, MSc, MBA ,&nbsp;Maria J. Gutierrez MD, MHS, MBA","doi":"10.1016/j.jaci.2025.04.034","DOIUrl":"10.1016/j.jaci.2025.04.034","url":null,"abstract":"<div><h3>Background</h3><div>Early infancy is marked by high susceptibility to severe viral respiratory infections and reduced protective antibody responses, making rapid development of local airway immunity essential. Despite this, the developmental dynamics of human airway B cells and their interaction with airway epithelial cells (AECs) in early life remain poorly understood.</div></div><div><h3>Objective</h3><div>We studied the developmental dynamics of human airway B-cell populations, the variation in AEC-derived B-cell survival and maturation factors with age, and how viral respiratory infections influence their production.</div></div><div><h3>Methods</h3><div>Changes in human airway B-cell populations and survival receptors across different pediatric age groups were analyzed by using a single-cell RNA sequencing dataset. The production of B-cell activating factor (BAFF) and other B-cell survival and maturation factors by human AECs was assessed in infants (&lt;12 months) and older children, both at baseline and after viral stimulation <em>in vitro.</em> Additional <em>in vivo</em> validation studies assessed airway BAFF production at baseline and during PCR-confirmed viral respiratory infections across pediatric age groups.</div></div><div><h3>Results</h3><div>We observed age-dependent shifts in airway B-cell composition, identifying the BAFF/BAFF-receptor axis as critical for B-cell maturation and survival in early life. Although BAFF production in AECs is initially reduced in infants (&lt;12 months), it can be activated by viral stimuli both <em>in vivo</em> and <em>in vitro.</em> Mechanistic studies showed that BAFF production in human infant AECs is induced by type I and III interferons via JAK/STAT signaling.</div></div><div><h3>Conclusion</h3><div>Human AEC JAK/STAT signaling activation regulates the early maturation of airway B-cell responses via local BAFF induction, particularly during viral infections.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 1082-1094"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130756","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}

{"title":"Brief Overview of This Month's JACI","authors":"","doi":"10.1016/S0091-6749(25)00902-9","DOIUrl":"10.1016/S0091-6749(25)00902-9","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages A1-A2"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204507","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}

{"title":"Loss of apolipoprotein E contributes to inflammatory macrophage activation and ferroptosis in NSAID-exacerbated respiratory disease","authors":"Gilles Schmiz ,&nbsp;Pascal Haimerl PhD ,&nbsp;Isika Ram MSc ,&nbsp;Manuel Kulagin ,&nbsp;Benedikt Spitzlberger MSc ,&nbsp;Fiona D.R. Henkel PhD ,&nbsp;Franziska Hartung PhD ,&nbsp;Sonja Schindela ,&nbsp;Zhigang Rao PhD ,&nbsp;Andreas Koeberle PhD ,&nbsp;Carsten B. Schmidt-Weber PhD ,&nbsp;Adam M. Chaker MD ,&nbsp;Antonie Lechner PhD ,&nbsp;Julia Esser-von Bieren PhD","doi":"10.1016/j.jaci.2025.06.010","DOIUrl":"10.1016/j.jaci.2025.06.010","url":null,"abstract":"<div><h3>Background</h3><div>Nonsteroidal anti-inflammatory drug–exacerbated respiratory disease (N-ERD) is characterized by chronic asthma, nasal polyposis, and intolerance of nonsteroidal anti-inflammatory drugs. We recently described aberrant macrophage activation and lipid metabolism in N-ERD; however, local drivers of nasal inflammation in N-ERD are incompletely understood.</div></div><div><h3>Objective</h3><div>Our aim was to study how apolipoprotein E (ApoE) deficiency in the N-ERD nasal mucosa affects the cross talk and inflammatory activation of macrophages and epithelial cells.</div></div><div><h3>Methods</h3><div>We combined transcriptional and mediator analysis of samples from patients with N-ERD and primary human cell culture to study ApoE in epithelial and myeloid cells.</div></div><div><h3>Results</h3><div>Nasal scrapings from patients with N-ERD exhibited decreased <em>APOE</em> expression compared with that exhibited by nasal mucosa of healthy individuals, but <em>APOE</em> was inherently low in epithelial cells. Instead, myeloid cells expressed highly abundant <em>APOE</em>, which was reduced in monocyte-derived macrophages from patients with N-ERD. Small interfering RNA–mediated knockdown of <em>APOE</em> in monocyte-derived macrophages resulted in increased expression of CXCL7, an inflammatory chemokine implicated in N-ERD. In addition, highly oxidized arachidonyl-phosphatidylethanolamine accumulated in <em>APOE</em>-knockdown macrophages, and ApoE protected macrophages from ferroptotic cell death.</div></div><div><h3>Conclusion</h3><div>Our results suggest a role for myeloid ApoE in regulating the cross talk between macrophages and epithelial cells, as well as in ferroptosis during type 2 airway inflammation. ApoE deficiency may thus contribute to chronic type 2 inflammation in patients with N-ERD, and its restoration could help reestablish normal epithelial barrier integrity and macrophage effector functions.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 1095-1102.e4"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337502","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}

{"title":"Heterozygous loss of MAP4K1 causes immune dysregulation by amplifying T-cell responses","authors":"Meri Kaustio PhD ,&nbsp;Monika Szymanska PhD ,&nbsp;Weiwei Li MSc ,&nbsp;Ragnhild Braathen MSc ,&nbsp;Tessa M. Campbell PhD ,&nbsp;Frida L. Haugen MSc ,&nbsp;Shiva Dahal-Koirala PhD ,&nbsp;Kristiina Silventoinen MD ,&nbsp;Katariina Nurmi PhD ,&nbsp;Matas Dinius BSc ,&nbsp;Kirsten Nowlan MSc ,&nbsp;Iivo Hetemäki MD, PhD ,&nbsp;Pu Chen MSc ,&nbsp;Katariina Mamia MSc ,&nbsp;Mikko R.J. Seppänen MD, PhD ,&nbsp;Juha Grönholm MD, PhD ,&nbsp;Eliisa Kekäläinen MD, PhD ,&nbsp;Emma M. Haapaniemi MD, PhD ,&nbsp;Kristiina Aalto MD, PhD ,&nbsp;Timi Martelius MD, PhD ,&nbsp;Janna Saarela MD, PhD","doi":"10.1016/j.jaci.2025.07.010","DOIUrl":"10.1016/j.jaci.2025.07.010","url":null,"abstract":"<div><h3>Background</h3><div><em>MAP4K1</em> encodes hematopoietic progenitor kinase 1 (HPK1), a serine/threonine kinase that negatively regulates T-cell receptor signaling via phosphorylation of the adaptor proteins SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kDa) and Gads. While common <em>MAP4K1</em> variants have been implicated in polygenic immune-mediated diseases, the impact of rare germline variants on human immunity remains undefined.</div></div><div><h3>Objective</h3><div>We investigated the immunologic and functional consequences of HPK1 deficiency in individuals with suspected inborn errors of immunity.</div></div><div><h3>Methods</h3><div>We performed genomic linkage analysis and exome sequencing to identify disease-associated variants in patients with inborn errors of immunity. Immunophenotyping, RNA sequencing, and functional assays were conducted on patient-derived lymphocytes, complemented by CRISPR-Cas9–mediated <em>MAP4K1</em> disruption and correction in primary T cells.</div></div><div><h3>Results</h3><div>Heterozygous <em>MAP4K1</em> loss-of-function variants were identified in two kindreds presenting with diverse immune dysregulatory symptoms, including recurrent fevers, inflammatory arthritis, Epstein-Barr virus–related complications, and nephritis. These variants led to reduced HPK1 protein levels and SLP-76^Ser376 phosphorylation. While lymphocyte development was largely preserved, T cells from HPK1-deficient individuals displayed hyperresponsiveness to T-cell receptor stimulation, characterized by elevated secretion of proinflammatory cytokines, particularly IFN-γ and TNF. CRISPR-Cas9–mediated knockout recapitulated, and variant correction partially reversed this phenotype. Transcriptomic profiling of stimulated CD4⁺ T cells further revealed upregulation of immune signaling pathways—including NF-κB, JAK/STAT, and AP-1—as well as increased expression of multiple T-cell cytokines, consistent with enhanced T-cell receptor signaling and T-cell responses in HPK1-deficient individuals.</div></div><div><h3>Conclusion</h3><div>HPK1 deficiency, caused by heterozygous loss of <em>MAP4K1,</em> is a novel monogenic cause of immune dysregulation. Increased T-cell activation and proinflammatory cytokine production are implicated in disease pathogenesis.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 1024-1037"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719909","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}

{"title":"Role of APE1 redox function in chronic rhinosinusitis pathogenesis: Implications for targeted therapy","authors":"Xiaojun Zhang MD, PhD ,&nbsp;Jie Zhang MMc ,&nbsp;Changhua Wu MMed ,&nbsp;Zhaochao Liu MMc ,&nbsp;Wensi Wu MD, PhD ,&nbsp;Lijie Qi MD, PhD ,&nbsp;Xinyu Xie MBBS ,&nbsp;Pin Wang PhD ,&nbsp;Yan Yuan PhD ,&nbsp;Xin Feng MD, PhD","doi":"10.1016/j.jaci.2025.07.004","DOIUrl":"10.1016/j.jaci.2025.07.004","url":null,"abstract":"<div><h3>Background</h3><div>APE1 is a multifunctional enzyme with 2 distinct functions—endonuclease activity in its C-terminal domain and redox function in its N-terminal domain. The redox activity of APE1 regulates a subset of transcription factors involved in cell survival, angiogenesis, and inflammation. However, its role in chronic rhinosinusitis (CRS) with nasal polyps is not fully understood.</div></div><div><h3>Objective</h3><div>We sought to elucidate the role of APE1 redox function in the pathogenesis of CRS and to evaluate the therapeutic potential of targeting APE1 with redox inhibitors.</div></div><div><h3>Methods</h3><div>APE1 expression and function were assessed in human nasal tissues using single-cell RNA sequencing, immunohistochemistry, Western blot, and quantitative RT-PCR. CRS mouse model, air-liquid interface–cultured human nasal epithelial cells, and BEAS-2B cells were used to examine the impact of the APE1 redox inhibitor on type 2 immune responses, mucus hypersecretion, epithelial barrier disruption, and oxidative stress.</div></div><div><h3>Results</h3><div>APE1 is highly expressed in patients with CRS with nasal polyps, and this upregulation was closely associated with eosinophil infiltration, mucus hypersecretion, epithelial damage, and oxidative stress. In the CRS mouse model and air-liquid interface–cultured human nasal epithelial cells, pharmacologic inhibition of APE1 redox function by C10 markedly reduced IL-25 production in tuft cells and decreased levels of type 2 cytokines (IL-4, IL-5, IL-13) along with T_H2 cell and group 2 innate lymphoid cell infiltration. Transcriptome analysis and <em>in vitro</em> experiments demonstrate that targeting APE1 effectively mitigates reactive oxygen species generation, oxidative stress imbalance, and mitochondrial damage.</div></div><div><h3>Conclusion</h3><div>The findings underscore the potential role of APE1 redox function in CRS pathophysiology, particularly in driving type 2 inflammation, mitochondrial oxidative stress, mucus production, and epithelial barrier dysfunction. The APE1 redox inhibitor, C10, effectively blocked type 2 inflammation and improved CRS pathology, suggesting its therapeutic potential for CRS treatment.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 948-965"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664183","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}

{"title":"Artificial intelligence in atopic dermatitis: A narrative review","authors":"Daniel Liu BA ,&nbsp;Benjamin D. Hu BS ,&nbsp;Jacob Glickman MD,&nbsp;Ross O’Hagan MD,&nbsp;Helen He MD,&nbsp;Emma Guttman-Yassky MD, PhD","doi":"10.1016/j.jaci.2025.06.028","DOIUrl":"10.1016/j.jaci.2025.06.028","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic, inflammatory skin condition characterized by substantial clinical heterogeneity, posing significant challenges to clinicians in diagnosis, severity stratification, and management. Artificial intelligence (AI) has emerged as a transformative tool in medicine and dermatology, offering innovative solutions for disease screening, severity grading, and personalized therapeutic optimization. In AD, machine learning models have been utilized to identify novel biomarkers for therapeutic development, leading to more effective, safer, and AD-specific therapies. Additionally, these models have demonstrated the ability to diagnose AD and differentiate it from other dermatologic conditions, reducing reliance on subjective clinical assessments. Future integration of AI tools into clinical practice, such as leveraging real-time transcriptomic and proteomic data to predict optimal therapeutics, monitor treatment responses, and develop AI-embedded wearable technology for remote and continuous disease monitoring, can rapidly transform AD management. However, as technology advances, ensuring bias reduction through representative training data sets and establishing proper regulatory oversight to protect patient safety and privacy will be critical for its successful and widespread adoption. As AI continues to revolutionize AD management, its integration into clinical practice holds the potential to improve diagnostic accuracy, enhance personalized treatment approaches, and bridge health care disparities, ultimately improving human health.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 889-898"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594429","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}

{"title":"Probing the diagnosis of SCID through in vitro T-cell development: Experience in 2 centers in North America","authors":"Clara Soulard MSc ,&nbsp;Francesca Pala PhD ,&nbsp;Marita Bosticardo PhD ,&nbsp;Elie Haddad PhD","doi":"10.1016/j.jaci.2025.04.021","DOIUrl":"10.1016/j.jaci.2025.04.021","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 906-908"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889293","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}

{"title":"Thymic pioneers: Charting the origin, identity, and fate of human thymus seeding progenitors","authors":"Kai Ling Liang PhD ,&nbsp;Lena Boehme PhD ,&nbsp;Silke Paepens MSc ,&nbsp;Maryam Hassan MSc ,&nbsp;Tom Taghon PhD","doi":"10.1016/j.jaci.2025.06.014","DOIUrl":"10.1016/j.jaci.2025.06.014","url":null,"abstract":"<div><div>T cells develop in the specialized microenvironment of the thymus but originate from hematopoietic stem cells in the bone marrow. Particularly in human, the identity and characteristics of the precursor cells that travel through the circulation to seed the thymic tissue remains a matter of debate, and the hematopoietic lineage potential and eventual intrathymic differentiation trajectories have not been fully defined. In addition, the mechanisms regulating the homing and entry process in the thymus are largely unclear but may have critical translational implications for thymic rejuvenation and efficient T-cell generation in immunocompromised individuals. In this review, we discuss the current understanding of human thymus seeding progenitor biology, explore how the thymic microenvironment may contribute to diverging fates between different thymus seeding populations, and discuss relevant knowledge gaps that could guide further fundamental and applied research to harness the power of thymus seeding progenitors to advance human health.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 854-866"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488038","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}