{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:30:09Z","timestamp":1777894209968,"version":"3.51.4"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.intimp.2025.115880","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:43:12Z","timestamp":1764225792000},"page":"115880","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"P2","title":["L-Citrulline inhibits Th2 cell activation via PLAC8 mediated autophagy and L-Citrulline depletion to alleviate pediatric asthma"],"prefix":"10.1016","volume":"168","author":[{"given":"Tian","family":"Tian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangli","family":"Jing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"10","key":"10.1016\/j.intimp.2025.115880_bb0005","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1167\/iovs.64.10.30","article-title":"Blocking Th2 signaling pathway alleviates the clinical symptoms and inflammation in allergic conjunctivitis","volume":"64","author":"Tao","year":"2023","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"4","key":"10.1016\/j.intimp.2025.115880_bb0010","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3390\/biom12040553","article-title":"Therapeutic potential for intractable asthma by targeting L-type amino acid transporter 1","volume":"12","author":"Hayashi","year":"2022","journal-title":"Biomolecules"},{"issue":"12","key":"10.1016\/j.intimp.2025.115880_bb0015","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-005668","article-title":"Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer","volume":"10","author":"Mao","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.intimp.2025.115880_bb0020","doi-asserted-by":"crossref","first-page":"1027551","DOI":"10.3389\/fonc.2023.1207551","article-title":"PLAC8 is an innovative biomarker for immunotherapy participating in remodeling the immune microenvironment of renal clear cell carcinoma","volume":"13","author":"Sun","year":"2023","journal-title":"Front. Oncol."},{"key":"10.1016\/j.intimp.2025.115880_bb0025","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.canlet.2017.08.023","article-title":"Induction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis","volume":"408","author":"Venkatesh","year":"2017","journal-title":"Cancer Lett."},{"key":"10.1016\/j.intimp.2025.115880_bb0030","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.virol.2021.10.001","article-title":"PLAC8 promotes EV71 infected inflammatory lesion by disturbing Th-cell-related cytokines release in neonatal mouse","volume":"564","author":"Yang","year":"2021","journal-title":"Virology"},{"issue":"1","key":"10.1016\/j.intimp.2025.115880_bb0035","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.immuni.2019.05.014","article-title":"Single-cell RNA sequencing of the T helper cell response to house dust mites defines a distinct gene expression signature in airway Th2 cells","volume":"51","author":"Christopher","year":"2019","journal-title":"Immunity"},{"key":"10.1016\/j.intimp.2025.115880_bb0040","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellimm.2021.104341","article-title":"Lipid metabolism in asthma: immune regulation and potential therapeutic target","volume":"364","author":"Li","year":"2021","journal-title":"Cell. Immunol."},{"issue":"1","key":"10.1016\/j.intimp.2025.115880_bb0045","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40104-022-00675-6","article-title":"Functional roles of taurine, L-theanine, L-citrulline, and betaine during heat stress in poultry","volume":"13","author":"Uyanga","year":"2022","journal-title":"J Anim Sci Biotechnol."},{"issue":"3","key":"10.1016\/j.intimp.2025.115880_bb0050","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.nut.2012.07.002","article-title":"Citrulline: from metabolism to therapeutic use","volume":"29","author":"Bahri","year":"2013","journal-title":"Nutrition"},{"issue":"1","key":"10.1016\/j.intimp.2025.115880_bb0055","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4103\/0972-9062.325640","article-title":"Administration of L-citrulline prevents plasmodium growth by inhibiting\/modulating T-regulatory cells during malaria pathogenesis","volume":"59","author":"Awasthi","year":"2022","journal-title":"J. Vector Borne Dis."},{"key":"10.1016\/j.intimp.2025.115880_bb0060","article-title":"ECHO-CREW investigators","volume":"10","author":"Snyder","year":"2022","journal-title":"Association of citrulline concentration at birth with lower respiratory tract infection in infancy: Findings from a multi-site birth cohort study, Front Pediatr"},{"issue":"4","key":"10.1016\/j.intimp.2025.115880_bb0065","doi-asserted-by":"crossref","first-page":"476","DOI":"10.3390\/nu16040476","article-title":"Antenatal growth, gestational age, birth, enteral feeding, and blood Citrulline levels in very low birth weight infants","volume":"16","author":"Obayashi","year":"2024","journal-title":"Nutrients"},{"key":"10.1016\/j.intimp.2025.115880_bb0070","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.3389\/fimmu.2018.02911","article-title":"L-arginine and L-Citrulline supplementation have different programming effect on regulatory T-cells function of infantile rats","volume":"9","author":"Lee","year":"2018","journal-title":"Front. Immunol."},{"issue":"6","key":"10.1016\/j.intimp.2025.115880_bb0075","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.109101","article-title":"Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation","volume":"35","author":"Crump","year":"2021","journal-title":"Cell Rep."},{"issue":"3","key":"10.1016\/j.intimp.2025.115880_bb0080","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2021.12.006","article-title":"Citrulline depletion by ASS1 is required for proinflammatory macrophage activation and immune responses","volume":"82","author":"Mao","year":"2022","journal-title":"Mol. Cell"},{"key":"10.1016\/j.intimp.2025.115880_bb0085","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-3-319-47656-8_2","article-title":"Collection and preparation of clinical samples for metabolomics","volume":"965","author":"Chetwynd","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.intimp.2025.115880_bb0090","doi-asserted-by":"crossref","DOI":"10.7717\/peerj.16684","article-title":"Dose-response effect of L-citrulline on skeletal muscle damage after acute eccentric exercise: an in vivo study in mice","volume":"11","author":"Ghozali","year":"2023","journal-title":"PeerJ"},{"issue":"4","key":"10.1016\/j.intimp.2025.115880_bb0095","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/ajh\/hps052","article-title":"The effects of short term L-citrulline supplementation on wave reflection responses to cold exposure with concurrent isometric exercise","volume":"26","author":"Sanchez-Gonzalez","year":"2013","journal-title":"Am. J. Hypertens."},{"issue":"2","key":"10.1016\/j.intimp.2025.115880_bb0100","first-page":"428","article-title":"Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs","volume":"92","author":"Imanaka","year":"2001","journal-title":"Anesth. Analg."},{"issue":"49","key":"10.1016\/j.intimp.2025.115880_bb0105","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/cea.13374","article-title":"T cells in severe childhood asthma. Clinical and experimental allergy","volume":"5","author":"Paul","year":"2019","journal-title":"Clin. Exp. Allergy"},{"issue":"8","key":"10.1016\/j.intimp.2025.115880_bb0110","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1084\/jem.20151448","article-title":"Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection","volume":"213","author":"Wilhelm","year":"2016","journal-title":"J. Exp. Med."},{"issue":"9","key":"10.1016\/j.intimp.2025.115880_bb0115","first-page":"1884","article-title":"Eosinophil cationic protein variation in patients with asthma and CRSwNP treated with Dupilumab","volume":"13","author":"Ledda","year":"2023","journal-title":"Life (Basel)."},{"issue":"1","key":"10.1016\/j.intimp.2025.115880_bb0120","doi-asserted-by":"crossref","DOI":"10.1088\/1752-7163\/acfbf1","article-title":"SNPs inFAM13AandIL2RBgenes are associated with FeNO in adult subjects with asthma","volume":"18","author":"Accordini","year":"2023","journal-title":"J. Breath Res."},{"issue":"5","key":"10.1016\/j.intimp.2025.115880_bb0125","doi-asserted-by":"crossref","first-page":"2300558","DOI":"10.1183\/13993003.00558-2023","article-title":"Dupilumab leads to better-controlled asthma & quality of life in children: the VOYAGE study","volume":"62","author":"Fiocchi","year":"2023","journal-title":"Eur. Respir. J."},{"issue":"11","key":"10.1016\/j.intimp.2025.115880_bb0130","doi-asserted-by":"crossref","first-page":"4116","DOI":"10.3390\/nu13114116","article-title":"Dysregulated arginine metabolism in Young patients with chronic persistent asthma and in human bronchial epithelial cells","volume":"13","author":"Zhou","year":"2021","journal-title":"Nutrients"},{"issue":"9","key":"10.1016\/j.intimp.2025.115880_bb0135","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.1002\/fsn3.2439","article-title":"L-citrulline inhibits body weight gain and hepatic fat accumulation by improving lipid metabolism in a rat nonalcoholic fatty liver disease model","volume":"69","author":"Kudo","year":"2021","journal-title":"Food Sci. Nutr."},{"issue":"3","key":"10.1016\/j.intimp.2025.115880_bb0140","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.3390\/nu7031426","article-title":"Arginine and citrulline and the immune response in sepsis","volume":"7","author":"Wijnands","year":"2015","journal-title":"Nutrients"},{"issue":"1","key":"10.1016\/j.intimp.2025.115880_bb0145","doi-asserted-by":"crossref","first-page":"L60","DOI":"10.1152\/ajplung.00194.2003","article-title":"Arginase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells","volume":"287","author":"Chicoine","year":"2004","journal-title":"Am J Physiol Lung Cell Mol."},{"issue":"4","key":"10.1016\/j.intimp.2025.115880_bb0150","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1002\/eji.1830250436","article-title":"Reciprocal regulation of the nitric oxide synthase\/arginase balance in mouse bone marrow-derived macrophages by Th1 and Th2 cytokines","volume":"25","author":"Modolell","year":"1995","journal-title":"Eur. J. Immunol."},{"issue":"1","key":"10.1016\/j.intimp.2025.115880_bb0155","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3945\/ajcn.2007.25765","article-title":"Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production","volume":"89","author":"Luiking","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.intimp.2025.115880_bb0160","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0037439","article-title":"Citrulline a more suitable substrate than arginine to restore no production and the microcirculation during endotoxemia","volume":"7","author":"Wijnands","year":"2012","journal-title":"PloS One"},{"issue":"7","key":"10.1016\/j.intimp.2025.115880_bb0165","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","article-title":"Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins","volume":"136","author":"Mosmann","year":"1986","journal-title":"J. Immunol."},{"key":"10.1016\/j.intimp.2025.115880_bb0170","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of effector CD4 T cell populations (*)","volume":"28","author":"Zhu","year":"2010","journal-title":"Annu. Rev. Immunol."},{"issue":"8","key":"10.1016\/j.intimp.2025.115880_bb0175","doi-asserted-by":"crossref","DOI":"10.1002\/eji.70021","article-title":"PD-L2 inhibits protective immunity, Th2 cell functional quality, and GATA-3 expression during filarial nematode infection","volume":"55","author":"Knipper","year":"2025","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.intimp.2025.115880_bb0180","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1146\/annurev-immunol-051116-052350","article-title":"Th2 cells in health and disease","volume":"35","author":"Nakayama","year":"2017","journal-title":"Annu. Rev. Immunol."},{"issue":"2","key":"10.1016\/j.intimp.2025.115880_bb0185","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nri2476","article-title":"GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation","volume":"9","author":"Ho","year":"2009","journal-title":"Nat. Rev. Immunol."},{"issue":"20","key":"10.1016\/j.intimp.2025.115880_bb0190","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222011079","article-title":"Clinical guidelines and new molecular targets for cutaneous lymphomas","volume":"22","author":"Sugaya","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"6","key":"10.1016\/j.intimp.2025.115880_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaci.2009.03.041","article-title":"IL-22-producing \u201cT22\u201d T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells","volume":"123","author":"Nograles","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"issue":"1","key":"10.1016\/j.intimp.2025.115880_bb0200","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/cr.2009.138","article-title":"Heterogeneity and plasticity of T helper cells","volume":"20","author":"Zhu","year":"2010","journal-title":"Cell Res."},{"key":"10.1016\/j.intimp.2025.115880_bb0205","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2020.101679","article-title":"Complex interplay between autophagy and oxidative stress in the development of pulmonary disease","volume":"36","author":"Ornatowski","year":"2020","journal-title":"Redox Biol."},{"issue":"14","key":"10.1016\/j.intimp.2025.115880_bb0210","doi-asserted-by":"crossref","first-page":"7778","DOI":"10.1111\/jcmm.15409","article-title":"Plac8-mediated autophagy regulates nasopharyngeal carcinoma cell function via AKT\/mTOR pathway","volume":"24","author":"Huang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"issue":"1","key":"10.1016\/j.intimp.2025.115880_bb0215","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s42003-024-07334-8","article-title":"PLAC8 attenuates pulmonary fibrosis and inhibits apoptosis of alveolar epithelial cells via facilitating autophagy","volume":"8","author":"Sun","year":"2025","journal-title":"Commun Biol."},{"issue":"21","key":"10.1016\/j.intimp.2025.115880_bb0220","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2022110727","article-title":"Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells","volume":"41","author":"Ugalde","year":"2022","journal-title":"EMBO J."},{"issue":"5","key":"10.1016\/j.intimp.2025.115880_bb0225","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.smim.2016.10.009","article-title":"Metabolic pathways in T cell activation and lineage differentiation","volume":"28","author":"Almeida","year":"2016","journal-title":"Seminars in immunology. Semin Immunol."},{"issue":"6","key":"10.1016\/j.intimp.2025.115880_bb0230","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/j.clnu.2017.10.009","article-title":"Citrulline in health and disease","volume":"37","author":"Papadia","year":"2018","journal-title":"Review on human studies, Clin Nutr."},{"issue":"2","key":"10.1016\/j.intimp.2025.115880_bb0235","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/all.14019","article-title":"LAT1-specific inhibitor is effective against T cell-mediated allergic skin inflammation","volume":"75","author":"Hayashi","year":"2020","journal-title":"Allergy"}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925018685?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925018685?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T07:14:01Z","timestamp":1777619641000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576925018685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":47,"alternative-id":["S1567576925018685"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2025.115880","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"L-Citrulline inhibits Th2 cell activation via PLAC8 mediated autophagy and L-Citrulline depletion to alleviate pediatric asthma","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2025.115880","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115880"}}