{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:30:00Z","timestamp":1788982200970,"version":"build-2803163510"},"reference-count":97,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["NE755\/6\u20101"],"award-info":[{"award-number":["NE755\/6\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Barrier\u2010forming olfactory glia cells, termed sustentacular cells, play important roles for immune defense of the olfactory mucosa, for example as entry sites for SARS\u2010CoV\u20102 and subsequent development of inflammation\u2010induced smell loss. Here we demonstrate that sustentacular cells express ACKR3, a chemokine receptor that functions both as a scavenger of the chemokine CXCL12 and as an activator of alternative signaling pathways. Differential gene expression analysis of bulk RNA sequencing data obtained from WT and ACKR3 conditional knockout mice revealed upregulation of genes involved in immune defense. To map the regulated genes to the different cell types of the olfactory mucosa, we employed biocomputational methods utilizing a single\u2010cell reference atlas. Transcriptome analysis, PCR and immunofluorescence identified up\u2010regulation of NF\u2010\u03baB\u2010related genes, known to amplify inflammatory signaling and to facilitate leukocyte transmigration, in the gliogenic lineage. Accordingly, we found a marked increase in leukocyte\u2010expressed genes and confirmed leukocyte infiltration into the olfactory mucosa. In addition, lack of ACKR3 led to enhanced expression and secretion of early mediators of immune defense by Bowman's glands. As a result, the number of apoptotic cells in the epithelium was decreased. In conclusion, our research underlines the importance of sustentacular cells in immune defense of the olfactory mucosa. Moreover, it identifies ACKR3, a druggable G protein\u2010coupled receptor, as a promising target for modulation of inflammation\u2010associated anosmia.<\/jats:p>","DOI":"10.1002\/glia.24527","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T12:55:01Z","timestamp":1710334501000},"page":"1183-1200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>ACKR3<\/scp> in olfactory glia cells shapes the immune defense of the olfactory mucosa"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9199-4746","authenticated-orcid":false,"given":"Andr\u00e9","family":"Dietz","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology, Jena University Hospital Friedrich Schiller University Jena  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Senf","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology, Jena University Hospital Friedrich Schiller University Jena  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3363-1231","authenticated-orcid":false,"given":"Eva M.","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology, Jena University Hospital Friedrich Schiller University Jena  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.104224"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-019-01785-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10862-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20110745"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.235018"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2920379"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801333RRR"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04643-1"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc5801"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-14426-4_11"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1995.tb00107.x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.8"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.06.032"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2018.0099"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12881"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620664114"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.08.011"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035114"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609067104"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12172164"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-12-86"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(199606)30:2<267::AID-NEU8>3.0.CO;2-3"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08574.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.add0484"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0146598"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18634-y"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-022-00937-4"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092310310"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1070230203"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300858"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40136-016-0114-4"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.116.023027"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20714"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.126"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20792"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201812310"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22735"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500747"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26325-4"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.3.7"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.02.013"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110330"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10772"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.118.115329"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad347"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01438"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01777.x"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjac024"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4507-09.2010"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-196618"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12777"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.63"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030711"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-104836"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200508-090JS"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1177\/019459989210600221"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.041703.084745"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20944"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.110.14.1635"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.10476"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2527-10.2010"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009175"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3544"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.062810"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22271"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21226"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912852107"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22477"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13091269"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29341-1"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12807"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.049"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.12.006"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.23073"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/19.6.671"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3338"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03100"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702229104"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjr063"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103412"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780221"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-9861(19961223)376:4<509::aid-cne1>3.0.co;2-5"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059547"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2640-16.2017"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01030-8"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1601-20.2021"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0585-y"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3769"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1442-3"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjad030"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T02:58:39Z","timestamp":1712804319000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.24527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":97,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/glia.24527"],"URL":"https:\/\/doi.org\/10.1002\/glia.24527","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"assertion":[{"value":"2024-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}