Journal of Allergy and Clinical Immunology最新文献

{"title":"Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses","authors":"","doi":"10.1016/j.jaci.2024.06.022","DOIUrl":"10.1016/j.jaci.2024.06.022","url":null,"abstract":"<div><h3>Background</h3><div>In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (<em>HTN1</em>) was found to be the most differentially downregulated gene in AFRS.</div></div><div><h3>Objective</h3><div>We sought to identify the molecular etiology of the downregulated expression of <em>HTN1</em>.</div></div><div><h3>Methods</h3><div>We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of T_H17/T_H22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls.</div></div><div><h3>Results</h3><div>We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22–producing T cells were deficient within sinus mucosa of AFRS patients. <em>In vitro</em> studies demonstrated a defect in IL-6/STAT3 signaling critical for T_H17/T_H22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating T_H17 cell abundance was normal.</div></div><div><h3>Conclusions</h3><div>Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6–dependent STAT3 phosphorylation that is critical for T_H17/T_H22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734208","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":"An in vitro study of the impact of IL-17A and IL-22 on ciliogenesis in nasal polyps epithelium via the Hippo-YAP pathway","authors":"","doi":"10.1016/j.jaci.2024.07.006","DOIUrl":"10.1016/j.jaci.2024.07.006","url":null,"abstract":"<div><h3>Background</h3><div>Cilia loss and impaired motile ciliary functions are among the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). IL17A and IL22 are the canonical cytokines of type 3 inflammation, exhibiting similar functional effects on epithelial cells. In this study, we sought to examine the effects of IL17A and IL22 on ciliated cells and investigate the potential involvement of Hippo-YAP signaling in their influence on ciliogenesis.</div></div><div><h3>Methods</h3><div>We assessed both the mRNA and protein expression levels of IL17A and IL22 in nasal tissues obtained from patients with CRSwNP and compared them to those from healthy controls. To further explore the impact of IL17A and IL22, we established a primary human nasal epithelial cell model using different concentrations (2 ng/mL, 10 ng/mL, 50 ng/mL) for a duration of 28 days in an air-liquid interface culture. Additionally, we employed the inhibitor verteporfin to investigate whether IL17A and IL22 exert their effects on ciliated cells via the Hippo-YAP pathway.</div></div><div><h3>Results</h3><div>The mRNA and protein levels of IL17A and IL22 in CRSwNP were significantly higher than those in healthy controls, revealing a robust correlation between IL17A and IL22. YAP was highly expressed in the nucleus of ciliated cells in CRSwNP and displayed a positive correlation with clinical symptoms. Both IL17A and IL22 were found to reduce the number of ciliated cells. IL17A, but not IL22, suppressed ciliogenesis by disrupting the proper development and docking of the basal body of ciliated cells, resulting in motile ciliary dysfunctions. Furthermore, the expression of YAP within the nucleus of ciliated cells gradually declined as these cells reached the final stage of differentiation. However, this process was obstructed by IL17A only. YAP inhibitors, such as verteporfin, markedly reversed the effects of IL17A by increasing the proportion of ciliated cells, suppressing nuclear YAP expression in these cells, and enhancing ciliary beating frequency.</div></div><div><h3>Conclusions</h3><div>Both IL17A and IL22 are overexpressed in nasal epithelium of CRSwNP, which is associated with the impairment of epithelial cell differentiation. Furthermore, IL17A has been shown to exert a disruptive effect on morphogenesis of motile cilia via activation of YAP.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734209","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":"Multiomics analysis identified IL-4–induced IL1RL1high eosinophils characterized by prominent cysteinyl leukotriene metabolism","authors":"","doi":"10.1016/j.jaci.2024.07.012","DOIUrl":"10.1016/j.jaci.2024.07.012","url":null,"abstract":"<div><h3>Background</h3><div>Clinical studies have demonstrated that IL-4, a type 2 cytokine, plays an important role in the pathogenesis of chronic rhinosinusitis and eosinophilic asthma. However, the direct effect of IL-4 on eosinophils remains unclear.</div></div><div><h3>Objective</h3><div>We aimed to elucidate the inflammatory effects of IL-4 on the functions of human eosinophils.</div></div><div><h3>Methods</h3><div>A multiomics analysis comprising transcriptomics, proteomics, lipidomics, quantitative RT-PCR, and flow cytometry was performed by using blood eosinophils from healthy subjects stimulated with IL-4, IL-5, or a combination thereof.</div></div><div><h3>Results</h3><div>Transcriptomic and proteomic analyses revealed that both IL-4 and IL-5 upregulate the expression of γ-gultamyl transferase 5, a fatty acid–metabolizing enzyme that converts leukotriene C₄ into leukotriene D₄. In addition, IL-4 specifically upregulates the expression of IL-1 receptor-like 1 (IL1RL1), a receptor for IL-33 and transglutaminase-2. Additional transcriptomic analysis of cells stimulated with IL-13 revealed altered gene expression profiles, characterized by the upregulation of γ-gultamyl transferase 5, transglutaminase-2, and IL1RL1. The IL-13–induced changes were not totally different from the IL-4–induced changes. Lipidomic analysis revealed that IL-5 and IL-4 additively increased the extracellular release of leukotriene D₄. <em>In vitro</em> experiments revealed that STAT6 and IL-4 receptor-α control the expression of these molecules in the presence of IL-4 and IL-13. Analysis of eosinophils derived from patients with allergic disorders indicated the involvement of IL-4 and IL-13 at the inflamed sites.</div></div><div><h3>Conclusions</h3><div>IL-4 induces the proallergic phenotype of IL1RL1^high eosinophils, with prominent cysteinyl leukotriene metabolism via STAT6. These cellular changes represent potential therapeutic targets for chronic rhinosinusitis and eosinophilic asthma.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788125","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}

{"title":"Trained immunity–based vaccines for infections and allergic diseases","authors":"","doi":"10.1016/j.jaci.2024.09.009","DOIUrl":"10.1016/j.jaci.2024.09.009","url":null,"abstract":"<div><div>Trained immunity has emerged as a new concept in immunology that is associated with the memory of innate immune cells and linked to specific metabolic and epigenetic reprogramming of these cells. Trained immunity may confer nonspecific and sustained protection against a broad range of pathogens, and recent findings show that it might also be involved in allergy mechanisms. Some conventional vaccines have demonstrated trained immunity induction as the mechanism underlying their heterologous protection. The development of novel vaccines designed especially for this purpose (trained immunity–based vaccines) might be useful in the absence of conventional vaccines or in specific clinical settings. Under certain circumstances, trained immunity could lead to persistent inflammatory innate immune cell responses in subjects with allergy, which could be associated with the development and worsening of allergy by promoting and amplifying aberrant type 2 immune responses. In other cases, trained immunity may help promote healthy immune responses to allergens, such as type 1 responses that counterbalance the type 2 inflammation or regulatory T cells that induce tolerance. Trained immunity–based allergen vaccines could become the next generation of allergen-specific immunotherapy vaccines, harnessing the potential of trained immunity to induce allergen tolerance. The identification and characterization of proper training inducers might well pave the way for the development of novel immunotherapies.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275157","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}

{"title":"Beyond IL-5 inhibition for the treatment of episodic angioedema with eosinophilia (Gleich syndrome)","authors":"","doi":"10.1016/j.jaci.2024.04.033","DOIUrl":"10.1016/j.jaci.2024.04.033","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276874","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":"Trained innate immunity: Concept, nomenclature, and future perspectives","authors":"","doi":"10.1016/j.jaci.2024.09.005","DOIUrl":"10.1016/j.jaci.2024.09.005","url":null,"abstract":"<div><div>During the past decade, compelling evidence has accumulated demonstrating that innate immune cells can mount adaptive characteristics, leading to long-term changes in their function. This <em>de facto</em> innate immune memory has been termed <em>trained immunity</em>. Trained immunity, which is mediated through extensive metabolic rewiring and epigenetic modifications, has important effects in human diseases. Although the upregulation of trained immunity by certain vaccines provides heterologous protection against infections, the inappropriate activation of trained immunity by endogenous stimuli contributes to the pathogenesis of inflammatory and neurodegenerative disorders. Development of vaccines that can induce both classical adaptive immunity and trained immunity may lead to a new generation of vaccines with increased efficacy. Activation of trained immunity can also lead to novel strategies for the treatment of cancer, whereas modulation of trained immunity can provide new approaches to the treatment of inflammatory diseases.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287880","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}

{"title":"CME Calendar-AAAAI","authors":"","doi":"10.1016/S0091-6749(24)01001-7","DOIUrl":"10.1016/S0091-6749(24)01001-7","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593002","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":"The Editors’ Choice","authors":"","doi":"10.1016/j.jaci.2024.09.015","DOIUrl":"10.1016/j.jaci.2024.09.015","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593049","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":"Mucosal trained immunity–based vaccines: Cutting recurrent infections in autoimmune patients on immunosuppression","authors":"","doi":"10.1016/j.jaci.2024.09.011","DOIUrl":"10.1016/j.jaci.2024.09.011","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287876","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(24)00995-3","DOIUrl":"10.1016/S0091-6749(24)00995-3","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592898","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}