Cellular &Molecular Immunology最新文献

{"title":"Fueling defense: PPARα enhances macrophage inflammatory responses","authors":"Marten A. Hoeksema","doi":"10.1038/s41423-025-01265-y","DOIUrl":"10.1038/s41423-025-01265-y","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"461-462"},"PeriodicalIF":21.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603799","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":"Systematic mining and quantification reveal the dominant contribution of non-HLA variations to acute graft-versus-host disease.","authors":"Shuang Liang, Yu-Jian Kang, Mingrui Huo, De-Chang Yang, Min Ling, Keli Yue, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Chen-Rui Xia, Jing-Yi Li, Ning Wu, Ruoyang Liu, Xinyu Dong, Jiangying Liu, Ge Gao, Xiao-Jun Huang","doi":"10.1038/s41423-025-01273-y","DOIUrl":"10.1038/s41423-025-01273-y","url":null,"abstract":"<p><p>Human leukocyte antigen (HLA) disparity between donors and recipients is a key determinant triggering intense alloreactivity, leading to a lethal complication, namely, acute graft-versus-host disease (aGVHD), after allogeneic transplantation. Moreover, aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation. Protocols for HLA-haploidentical hematopoietic cell transplantation (haploHCT) have been established successfully and widely applied, further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD. On the basis of our time-consecutive large haploHCT cohort (with a homogenous discovery set and an extended confirmatory set), we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors. In addition to identifying multiple loss-of-function (LoF) risk variations in non-HLA coding genes, our data-driven study revealed that non-HLA genetic variations, independent of HLA disparity, contributed the most to the occurrence of aGVHD. This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT. Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells. Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540287","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":"Cholesterol homeostasis and lipid raft dynamics at the basis of tumor-induced immune dysfunction in chronic lymphocytic leukemia.","authors":"Chaja F Jacobs, Fleur S Peters, Elena Camerini, Gaspard Cretenet, Joanne Rietveld, Bauke V Schomakers, Michel van Weeghel, Nico Hahn, Sanne G S Verberk, Jan Van den Bossche, Mirjam Langeveld, Fleur Kleijwegt, Eric Eldering, Noam Zelcer, Arnon P Kater, Helga Simon-Molas","doi":"10.1038/s41423-025-01262-1","DOIUrl":"https://doi.org/10.1038/s41423-025-01262-1","url":null,"abstract":"<p><p>Autologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction prevails. In CLL, disturbed mitochondrial metabolism has been linked to defective T-cell activation and proliferation. Recent research suggests that lipid metabolism regulates mitochondrial function and differentiation in T cells, yet its role in CLL remains unexplored. This comprehensive study compares T-cell lipid metabolism in CLL patients and healthy donors, revealing critical dependence on exogenous cholesterol for human T-cell expansion following TCR-mediated activation. Using multi-omics and functional assays, we found that T cells present in viably frozen samples of patients with CLL (CLL T cells) showed impaired adaptation to cholesterol deprivation and inadequate upregulation of key lipid metabolism transcription factors. CLL T cells exhibited altered lipid storage, with increased triacylglycerols and decreased cholesterol, and inefficient fatty acid oxidation (FAO). Functional consequences of reduced FAO in T cells were studied using samples from patients with inherent FAO disorders. Reduced FAO was associated with lower T-cell activation but did not affect proliferation. This implicates low cholesterol levels as a primary factor limiting T-cell proliferation in CLL. CLL T cells displayed fewer and less clustered lipid rafts, potentially explaining the impaired immune synapse formation observed in these patients. Our findings highlight significant disruptions in lipid metabolism as drivers of functional deficiencies in CLL T cells, underscoring the pivotal role of cholesterol in T-cell proliferation. This study suggests that modulating cholesterol metabolism could enhance T-cell function in CLL, presenting novel immunotherapeutic approaches to improve outcome in this challenging disease.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540283","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":"GPNMB disrupts SNARE complex assembly to maintain bacterial proliferation within macrophages.","authors":"Zhenzhen Yan, Jinghong Han, Zihao Mi, Zhenzhen Wang, Yixuan Fu, Chuan Wang, Ningning Dang, Hong Liu, Furen Zhang","doi":"10.1038/s41423-025-01272-z","DOIUrl":"https://doi.org/10.1038/s41423-025-01272-z","url":null,"abstract":"<p><p>Xenophagy plays a crucial role in restraining the growth of intracellular bacteria in macrophages. However, the machinery governing autophagosome‒lysosome fusion during bacterial infection remains incompletely understood. Here, we utilize leprosy, an ideal model for exploring the interactions between host defense mechanisms and bacterial infection. We highlight the glycoprotein nonmetastatic melanoma protein B (GPNMB), which is highly expressed in macrophages from lepromatous leprosy (L-Lep) patients and interferes with xenophagy during bacterial infection. Upon infection, GPNMB interacts with autophagosomal-localized STX17, leading to a reduced N-glycosylation level at N296 of GPNMB. This modification promotes the degradation of SNAP29, thus preventing the assembly of the STX17-SNAP29-VAMP8 SNARE complex. Consequently, the fusion of autophagosomes with lysosomes is disrupted, resulting in inhibited cellular autophagic flux. In addition to Mycobacterium leprae, GPNMB deficiency impairs the proliferation of various intracellular bacteria in human macrophages, suggesting a universal role of GPNMB in intracellular bacterial infection. Furthermore, compared with their counterparts, Gpnmb^fl/fl Lyz2-Cre mice presented decreased Mycobacterium marinum amplification. Overall, our study reveals a previously unrecognized role of GPNMB in host antibacterial defense and provides insights into its regulatory mechanism in SNARE complex assembly.</p>","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556033","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":"On the origin of neutrophils","authors":"Leo Koenderman,&nbsp;Kiki Tesselaar,&nbsp;Nienke Vrisekoop","doi":"10.1038/s41423-025-01270-1","DOIUrl":"10.1038/s41423-025-01270-1","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"459-460"},"PeriodicalIF":21.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522763","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":"Inflammation-triggered Gli1+ stem cells engage with extracellular vesicles to prime aberrant neutrophils to exacerbate periodontal immunopathology","authors":"Xin-Yue Cai,&nbsp;Chen-Xi Zheng,&nbsp;Hao Guo,&nbsp;Si-Yuan Fan,&nbsp;Xiao-Yao Huang,&nbsp;Ji Chen,&nbsp;Jie-Xi Liu,&nbsp;Yu-Ru Gao,&nbsp;An-Qi Liu,&nbsp;Jia-Ning Liu,&nbsp;Xiao-Hui Zhang,&nbsp;Chao Ma,&nbsp;Hao Wang,&nbsp;Fei Fu,&nbsp;Peng Peng,&nbsp;Hao-Kun Xu,&nbsp;Bing-Dong Sui,&nbsp;Kun Xuan,&nbsp;Yan Jin","doi":"10.1038/s41423-025-01271-0","DOIUrl":"10.1038/s41423-025-01271-0","url":null,"abstract":"Periodontitis is a prevalent and progressive detrimental disease characterized by chronic inflammation, and the immunopathological mechanisms are not yet fully understood. Mesenchymal stem cells (MSCs) play crucial roles as immunoregulators and maintain tissue homeostasis and regeneration, but their in vivo function in immunopathology and periodontal tissue deterioration is still unclear. Here, we utilized multiple transgenic mouse models to specifically mark, ablate and modulate Gli1+ cells, a critical and representative subset of MSCs in the periodontium, to explore their specific role in periodontal immunopathology. We revealed that Gli1+ cells, upon challenge with an inflammatory microenvironment, significantly induce rapid trafficking and aberrant activation of neutrophils, thus exacerbating alveolar bone destruction. Mechanistically, extracellular vesicles (EVs) released by Gli1+ cells act as crucial immune regulators in periodontal tissue, mediating the recruitment and activation of neutrophils through increased neutrophil generation of reactive oxygen species and stimulation of nuclear factor kappa-B signaling. Furthermore, we discovered that CXC motif chemokine ligand 1 (CXCL1) is exposed on the surface of EVs derived from inflammation-challenged Gli1+ cells to prime aberrant neutrophils via the CXCL1-CXC motif chemokine receptor 2 (CXCR2) axis. Importantly, specific inhibition of EV release from Gli1+ cells or pharmacological therapy with GANT61 ameliorates periodontal inflammation and alveolar bone loss. Collectively, our findings identify previously unrecognized roles of Gli1+ cells in orchestrating infiltration and promoting aberrant activation of neutrophils under inflammation, which provides pathological insights and potential therapeutic targets for periodontitis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"371-389"},"PeriodicalIF":21.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522760","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":"Targeting macrophage polarization by inhibiting Pim2 alleviates inflammatory arthritis via metabolic reprogramming","authors":"Xiaojun Xu,&nbsp;Peitao Xu,&nbsp;Guozhen Shen,&nbsp;Xiaoshuai Peng,&nbsp;Zhidong Liu,&nbsp;Chaoqiang Chen,&nbsp;Wenhui Yu,&nbsp;Zepeng Su,&nbsp;Jiajie Lin,&nbsp;Guan Zheng,&nbsp;Guiwen Ye,&nbsp;Peng Wang,&nbsp;Zhongyu Xie,&nbsp;Yanfeng Wu,&nbsp;Huiyong Shen,&nbsp;Jinteng Li","doi":"10.1038/s41423-025-01268-9","DOIUrl":"10.1038/s41423-025-01268-9","url":null,"abstract":"Macrophage polarization and energy metabolic reprogramming play pivotal roles in the onset and progression of inflammatory arthritis. Moreover, although previous studies have reported that the proviral integration of Moloney virus 2 (Pim2) kinase is involved in various cancers through the mediation of aerobic glycolysis in cancer cells, its role in inflammatory arthritis remains unclear. In this study, we demonstrated that multiple metabolic enzymes are activated upon Pim2 upregulation during M1 macrophage polarization. Specifically, Pim2 directly phosphorylates PGK1-S203, PDHA1-S300, and PFKFB2-S466, thereby promoting glycolytic reprogramming. Pim2 expression was elevated in macrophages from patients with inflammatory arthritis and collagen-induced arthritis (CIA) model mice. Conditional knockout of Pim2 in macrophages or administration of the Pim2 inhibitor HJ-PI01 attenuated arthritis development by inhibiting M1 macrophage polarization. Through molecular docking and dynamic simulation, bexarotene was identified as an inhibitor of Pim2 that inhibits glycolysis and downstream M1 macrophage polarization, thereby mitigating the progression of inflammatory arthritis. For targeted treatment, neutrophil membrane-coated bexarotene (Bex)-loaded PLGA-based nanoparticles (NM@NP-Bex) were developed to slow the progression of inflammatory arthritis by suppressing the polarization of M1 macrophages, and these nanoparticles (NPs) exhibited superior therapeutic effects with fewer side effects. Taken together, the results of our study demonstrated that targeting Pim2 inhibition could effectively alleviate inflammatory arthritis via glycolysis inhibition and reversal of the M1/M2 macrophage imbalance. NM@NPs loaded with bexarotene could represent a promising targeted strategy for the treatment of inflammatory arthritis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"418-436"},"PeriodicalIF":21.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-025-01268-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499584","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":"Gut-derived macrophages link intestinal damage to brain injury after cardiac arrest through TREM1 signaling","authors":"Yuan Chang,&nbsp;Jiancong Chen,&nbsp;Yuqin Peng,&nbsp;Kunxue Zhang,&nbsp;Yuzhen Zhang,&nbsp;Xiaolin Zhao,&nbsp;Di Wang,&nbsp;Lei Li,&nbsp;Juan Zhu,&nbsp;Kewei Liu,&nbsp;Zhentong Li,&nbsp;Suyue Pan,&nbsp;Kaibin Huang","doi":"10.1038/s41423-025-01263-0","DOIUrl":"10.1038/s41423-025-01263-0","url":null,"abstract":"Brain injury is the leading cause of death and disability in survivors of cardiac arrest, where neuroinflammation triggered by infiltrating macrophages plays a pivotal role. Here, we seek to elucidate the origin of macrophages infiltrating the brain and their mechanism of action after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Wild-type or photoconvertible Cd68-Cre:R26-LSL-KikGR mice were subjected to 10-min CA/CPR, and the migration of gut-derived macrophages into brain was assessed. Transcriptome sequencing was performed to identify the key proinflammatory signal of macrophages infiltrating the brain, triggering receptor expressed on myeloid cells 1 (TREM1). Upon drug intervention, the effects of TREM1 on post-CA/CPR brain injury were further evaluated. 16S rRNA sequencing was used to detect gut dysbiosis after CA/CPR. Through photoconversion experiments, we found that small intestine-derived macrophages infiltrated the brain and played a crucial role in triggering secondary brain injury after CA/CPR. The infiltrating peripheral macrophages showed upregulated TREM1 levels, and we further revealed the crucial role of gut-derived TREM1+ macrophages in post-CA/CPR brain injury through a drug intervention targeting TREM1. Moreover, a close correlation between upregulated TREM1 expression and poor neurological outcomes was observed in CA survivors. Mechanistically, CA/CPR caused a substantial expansion of Enterobacter at the early stage, which ignited intestinal TREM1 signaling via the activation of Toll-like receptor 4 on macrophages through the release of lipopolysaccharide. Our findings reveal essential crosstalk between the gut and brain after CA/CPR and underscore the potential of targeting TREM1+ small intestine-derived macrophages as a novel therapeutic strategy for mitigating post-CA/CPR brain injury.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"437-455"},"PeriodicalIF":21.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472375","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":"β-hydroxybutyrylation and O-GlcNAc modifications of STAT1 modulate antiviral defense in aging","authors":"Yibo Zuo,&nbsp;Qin Wang,&nbsp;Wanying Tian,&nbsp;Zhijin Zheng,&nbsp;Wei He,&nbsp;Renxia Zhang,&nbsp;Qian Zhao,&nbsp;Ying Miao,&nbsp;Yukang Yuan,&nbsp;Jun wang,&nbsp;Hui Zheng","doi":"10.1038/s41423-025-01266-x","DOIUrl":"10.1038/s41423-025-01266-x","url":null,"abstract":"Aging changes the protein activity status to affect the body’s functions. However, how aging regulates protein posttranslational modifications (PTMs) to modulate the antiviral defense ability of the body remains unclear. Here, we found that aging promotes STAT1 β-hydroxybutyrylation (Kbhb) at Lys592, which inhibits the interaction between STAT1 and type-I interferon (IFN-I) receptor 2 (IFNAR2), thereby attenuating IFN-I-mediated antiviral defense activity. Additionally, we discovered that a small molecule from a plant source, hydroxy camptothecine, can effectively reduce the level of STAT1 Kbhb, thus increasing antiviral defense ability in vivo. Further studies revealed that STAT1 O-GlcNAc modifications at Thr699 block CBP-induced STAT1 Kbhb. Importantly, fructose can improve IFN-I antiviral defense activity by orchestrating STAT1 O-GlcNAc and Kbhb modifications. This study reveals the significance of the switch between STAT1 Kbhb and O-GlcNAc modifications in regulating IFN-I antiviral immunity during aging and provides potential strategies to improve the body’s antiviral defense ability in elderly individuals.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 4","pages":"403-417"},"PeriodicalIF":21.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467066","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":"Type 2 immunity in allergic diseases","authors":"Ismail Ogulur,&nbsp;Yasutaka Mitamura,&nbsp;Duygu Yazici,&nbsp;Yagiz Pat,&nbsp;Sena Ardicli,&nbsp;Manru Li,&nbsp;Paolo D’Avino,&nbsp;Carina Beha,&nbsp;Huseyn Babayev,&nbsp;Bingjie Zhao,&nbsp;Can Zeyneloglu,&nbsp;Oliva Giannelli Viscardi,&nbsp;Ozge Ardicli,&nbsp;Ayca Kiykim,&nbsp;Asuncion Garcia-Sanchez,&nbsp;Juan-Felipe Lopez,&nbsp;Li-li Shi,&nbsp;Minglin Yang,&nbsp;Stephan R. Schneider,&nbsp;Stephen Skolnick,&nbsp;Raja Dhir,&nbsp;Urszula Radzikowska,&nbsp;Abhijeet J. Kulkarni,&nbsp;Manal Bel Imam,&nbsp;Willem van de Veen,&nbsp;Milena Sokolowska,&nbsp;Mar Martin-Fontecha,&nbsp;Oscar Palomares,&nbsp;Kari C. Nadeau,&nbsp;Mubeccel Akdis,&nbsp;Cezmi A. Akdis","doi":"10.1038/s41423-025-01261-2","DOIUrl":"10.1038/s41423-025-01261-2","url":null,"abstract":"Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 3","pages":"211-242"},"PeriodicalIF":21.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-025-01261-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439559","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}