{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:06:50Z","timestamp":1789160810923,"version":"build-2803163510"},"reference-count":57,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Brain, Behavior, &amp; Immunity - Health"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.bbih.2026.101340","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:02:38Z","timestamp":1787641358000},"page":"101340","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["IL-33 as a boundary-tissue state-transfer signal: a Reader\u2013Alarmin\u2013Effector architecture linking CNS and skin"],"prefix":"10.1016","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8482-1687","authenticated-orcid":false,"given":"Tomohiko","family":"Nagasawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbih.2026.101340_bib1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1126\/science.aax6452","article-title":"Specialized cutaneous Schwann cells initiate pain sensation","volume":"365","author":"Abdo","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.bbih.2026.101340_bib2","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/j.jid.2016.01.030","article-title":"The alarmin IL-33 derived from HSV-2-infected keratinocytes triggers mast cell-mediated antiviral innate immunity","volume":"136","author":"Aoki","year":"2016","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.bbih.2026.101340_bib3","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.jid.2019.01.013","article-title":"Yin-Yang of IL-33 in human skin mast cells: reduced degranulation, but augmented histamine synthesis through p38 activation","volume":"139","author":"Babina","year":"2019","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.bbih.2026.101340_bib4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/j.1365-2133.1977.tb07152.x","article-title":"Epidermal 'turnover time' \u2014 a new examination","volume":"96","author":"Bergstresser","year":"1977","journal-title":"Br. J. Dermatol."},{"key":"10.1016\/j.bbih.2026.101340_bib5","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20250970","article-title":"Claudin-1-mediated positioning of DC1 to mTECs is essential for maintenance of central tolerance","volume":"223","author":"B\u0159ezina","year":"2026","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bbih.2026.101340_bib6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ajpath.2011.03.010","article-title":"The immune-modulating cytokine and endogenous alarmin interleukin-33 is upregulated in skin exposed to inflammatory UVB radiation","volume":"179","author":"Byrne","year":"2011","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.bbih.2026.101340_bib7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jaci.2014.11.037","article-title":"Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33","volume":"136","author":"Christianson","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.bbih.2026.101340_bib8","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jid.2021.05.033","article-title":"TSLP impairs epidermal barrier integrity by stimulating the formation of nuclear IL-33\/phosphorylated STAT3 complex in human keratinocytes","volume":"142","author":"Dai","year":"2022","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.bbih.2026.101340_bib9","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1016\/j.jid.2021.04.002","article-title":"Nuclear IL-33 plays an important role in the suppression of FLG, LOR, KRT1, and KRT10 by IL-4 and IL-13 in human keratinocytes","volume":"141","author":"Dai","year":"2021","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.bbih.2026.101340_bib10","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1089\/jir.2015.0159","article-title":"The expression and regulation of interleukin-33 in human epidermal keratinocytes: a new mediator of atopic dermatitis","volume":"36","author":"Du","year":"2016","journal-title":"J. Interferon Cytokine Res."},{"key":"10.1016\/j.bbih.2026.101340_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.pneurobio.2019.04.003","article-title":"Microglia: lifelong patrolling immune cells of the brain","volume":"179","author":"Eyo","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"10.1016\/j.bbih.2026.101340_bib12","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.immuni.2020.10.011","article-title":"The intersection of epigenetics and metabolism in trained immunity","volume":"54","author":"Fanucchi","year":"2021","journal-title":"Immunity"},{"key":"10.1016\/j.bbih.2026.101340_bib13","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/nn.4631","article-title":"Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging","volume":"20","author":"F\u00fcger","year":"2017","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.bbih.2026.101340_bib14","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.neuron.2015.01.013","article-title":"The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury","volume":"85","author":"Gadani","year":"2015","journal-title":"Neuron"},{"key":"10.1016\/j.bbih.2026.101340_bib15","doi-asserted-by":"crossref","first-page":"9765","DOI":"10.2147\/JIR.S478987","article-title":"Inflammatory memory in epidermal stem cells: a new strategy for recurrent inflammatory skin diseases","volume":"17","author":"Gao","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"10.1016\/j.bbih.2026.101340_bib16","doi-asserted-by":"crossref","first-page":"8765","DOI":"10.1073\/pnas.1601914113","article-title":"Alternative splicing of interleukin-33 and type 2 inflammation in asthma","volume":"113","author":"Gordon","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbih.2026.101340_bib17","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20220605","article-title":"Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice","volume":"220","author":"Han","year":"2023","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bbih.2026.101340_bib18","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41593-021-00905-6","article-title":"Neuroinflammatory astrocyte subtypes in the mouse brain","volume":"24","author":"Hasel","year":"2021","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.bbih.2026.101340_bib19","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.immuni.2021.12.001","article-title":"Disruption of the IL-33-ST2-AKT signaling axis impairs neurodevelopment by inhibiting microglial metabolic adaptation and phagocytic function","volume":"55","author":"He","year":"2022","journal-title":"Immunity"},{"key":"10.1016\/j.bbih.2026.101340_bib20","doi-asserted-by":"crossref","first-page":"7231","DOI":"10.1523\/JNEUROSCI.1709-08.2008","article-title":"STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury","volume":"28","author":"Herrmann","year":"2008","journal-title":"J. Neurosci."},{"key":"10.1016\/j.bbih.2026.101340_bib21","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1159\/000098163","article-title":"A keratinocyte's course of life","volume":"20","author":"Houben","year":"2007","journal-title":"Skin Pharmacol. Physiol."},{"key":"10.1016\/j.bbih.2026.101340_bib22","doi-asserted-by":"crossref","first-page":"eabc6259","DOI":"10.1126\/sciimmunol.abc6259","article-title":"Cellular context of IL-33 expression dictates impact on anti-helminth immunity","volume":"5","author":"Hung","year":"2020","journal-title":"Sci. Immunol."},{"key":"10.1016\/j.bbih.2026.101340_bib23","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jdermsci.2019.08.006","article-title":"Interleukin-33 in atopic dermatitis","volume":"96","author":"Imai","year":"2019","journal-title":"J. Dermatol. Sci."},{"key":"10.1016\/j.bbih.2026.101340_bib24","doi-asserted-by":"crossref","first-page":"13921","DOI":"10.1073\/pnas.1307321110","article-title":"Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice","volume":"110","author":"Imai","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbih.2026.101340_bib25","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1038\/s41590-024-01982-y","article-title":"MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33","volume":"25","author":"Inclan-Rico","year":"2024","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.bbih.2026.101340_bib26","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nature10851","article-title":"Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity","volume":"483","author":"Jiang","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.bbih.2026.101340_bib27","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1084\/jem.20091527","article-title":"External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers","volume":"206","author":"Kubo","year":"2009","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bbih.2026.101340_bib28","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/s41586-024-07187-5","article-title":"Disease-associated astrocyte epigenetic memory promotes CNS pathology","volume":"627","author":"Lee","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.bbih.2026.101340_bib29","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/j.jaci.2020.02.026","article-title":"ILC2 activation by keratinocyte-derived IL-25 drives IL-13 production at sites of allergic skin inflammation","volume":"145","author":"Leyva-Castillo","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.bbih.2026.101340_bib30","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.bbih.2026.101340_bib31","doi-asserted-by":"crossref","first-page":"5001","DOI":"10.3390\/ijms24055001","article-title":"Molecular mechanisms of neurogenic inflammation of the skin","volume":"24","author":"Marek-J\u00f3zefowicz","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.bbih.2026.101340_bib32","doi-asserted-by":"crossref","first-page":"10762","DOI":"10.1073\/pnas.1509070112","article-title":"IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions","volume":"112","author":"Monticelli","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbih.2026.101340_bib33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0003331","article-title":"The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'?","volume":"3","author":"Moussion","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.bbih.2026.101340_bib34","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nature24271","article-title":"Inflammatory memory sensitizes skin epithelial stem cells to tissue damage","volume":"550","author":"Naik","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.bbih.2026.101340_bib35","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.cell.2020.05.050","article-title":"Microglial remodeling of the extracellular matrix promotes synapse plasticity","volume":"182","author":"Nguyen","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.bbih.2026.101340_bib36","doi-asserted-by":"crossref","DOI":"10.1172\/JCI196108","article-title":"Dermal fibroblasts respond to IL-4 and IL-13 and promote T cell recruitment in atopic dermatitis","volume":"136","author":"Numata","year":"2026","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.bbih.2026.101340_bib37","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1016\/j.immuni.2022.09.016","article-title":"Interleukin-33-activated neuropeptide CGRP-producing memory Th2 cells cooperate with somatosensory neurons to induce conjunctival itch","volume":"55","author":"Okano","year":"2022","journal-title":"Immunity"},{"key":"10.1016\/j.bbih.2026.101340_bib38","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1084\/jem.20111718","article-title":"Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome","volume":"208","author":"Ouchi","year":"2011","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bbih.2026.101340_bib39","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.4049\/jimmunol.1101977","article-title":"Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues","volume":"188","author":"Pichery","year":"2012","journal-title":"J. Immunol."},{"key":"10.1016\/j.bbih.2026.101340_bib40","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbi.2014.08.002","article-title":"Interleukin-33 treatment reduces secondary injury and improves functional recovery after contusion spinal cord injury","volume":"44","author":"Pomeshchik","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.bbih.2026.101340_bib41","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jid.2025.08.016","article-title":"Nociceptive Schwann cells enter the sensory spotlight","volume":"146","author":"Reznik","year":"2026","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.bbih.2026.101340_bib42","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/jid.2011.446","article-title":"IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors","volume":"132","author":"Savinko","year":"2012","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.bbih.2026.101340_bib43","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009027","article-title":"Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling","volume":"16","author":"Still","year":"2020","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.bbih.2026.101340_bib44","doi-asserted-by":"crossref","first-page":"eabb7028","DOI":"10.1126\/scitranslmed.abb7028","article-title":"Long-term skin-resident memory T cells proliferate in situ and are involved in human graft-versus-host disease","volume":"12","author":"Strobl","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.bbih.2026.101340_bib45","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.alit.2022.04.003","article-title":"Peripheral itch sensitization in atopic dermatitis","volume":"71","author":"Tominaga","year":"2022","journal-title":"Allergol. Int."},{"key":"10.1016\/j.bbih.2026.101340_bib46","doi-asserted-by":"crossref","first-page":"7443","DOI":"10.3390\/ijms22147443","article-title":"Regulatory T cells exhibit interleukin-33-dependent migratory behavior during skin barrier disruption","volume":"22","author":"Toyama","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.bbih.2026.101340_bib47","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1126\/science.aal3589","article-title":"Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development","volume":"359","author":"Vainchtein","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.bbih.2026.101340_bib48","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.689346","article-title":"Pathological neuroinflammatory conversion of reactive astrocytes is induced by microglia and involves chromatin remodeling and triggered TLR4 signaling","volume":"12","author":"Villarreal","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.bbih.2026.101340_bib49","article-title":"Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus","volume":"118","author":"Wang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbih.2026.101340_bib50","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.115837","article-title":"The IL-33\/ST2 axis and tissue Treg maintain epithelial homeostasis and restrain cancer development in the skin","volume":"44","author":"Ward","year":"2025","journal-title":"Cell Rep."},{"key":"10.1016\/j.bbih.2026.101340_bib51","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2340\/00015555-3164","article-title":"European S2k Guideline on chronic pruritus","volume":"99","author":"Weisshaar","year":"2019","journal-title":"Acta Derm. Venereol."},{"key":"10.1016\/j.bbih.2026.101340_bib52","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1126\/science.abq4822","article-title":"Droplet-based forward genetic screening of astrocyte\u2013microglia cross-talk","volume":"379","author":"Wheeler","year":"2023","journal-title":"Science"},{"key":"10.1016\/j.bbih.2026.101340_bib53","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1523\/JNEUROSCI.3233-16.2017","article-title":"ST2\/IL-33-dependent microglial response limits acute ischemic brain injury","volume":"37","author":"Yang","year":"2017","journal-title":"J. Neurosci."},{"key":"10.1016\/j.bbih.2026.101340_bib54","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.molmed.2025.03.012","article-title":"Keratinocytes: new perspectives in inflammatory skin diseases","volume":"31","author":"Ye","year":"2025","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.bbih.2026.101340_bib55","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.jaci.2014.08.001","article-title":"Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis","volume":"134","author":"Yoshida","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.bbih.2026.101340_bib56","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/jdv.15973","article-title":"Neuroimmune interactions in chronic itch of atopic dermatitis","volume":"34","author":"Yosipovitch","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"10.1016\/j.bbih.2026.101340_bib57","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1111\/all.70284","article-title":"Epidermal PAR2-TRPV3-IL-33 signaling promotes mast cell recruitment and sensory nerve-mast cell interactions in atopic dermatitis","volume":"81","author":"Zhao","year":"2026","journal-title":"Allergy"}],"container-title":["Brain, Behavior, &amp; Immunity - Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666354626001730?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666354626001730?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:16:20Z","timestamp":1789157780000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666354626001730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":57,"alternative-id":["S2666354626001730"],"URL":"https:\/\/doi.org\/10.1016\/j.bbih.2026.101340","relation":{},"ISSN":["2666-3546"],"issn-type":[{"value":"2666-3546","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"IL-33 as a boundary-tissue state-transfer signal: a Reader\u2013Alarmin\u2013Effector architecture linking CNS and skin","name":"articletitle","label":"Article Title"},{"value":"Brain, Behavior, & Immunity - Health","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbih.2026.101340","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"101340"}}