{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T07:05:43Z","timestamp":1784703943777,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":201,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2706501"],"award-info":[{"award-number":["2023YFC2706501"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013105","name":"Shanghai Rising-Star Program","doi-asserted-by":"publisher","award":["22QA1401400"],"award-info":[{"award-number":["22QA1401400"]}],"id":[{"id":"10.13039\/501100013105","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    This study describes a case of severe congenital neutropenia (SCN) harboring biallelic\n                    <jats:italic>CSF3R<\/jats:italic>\n                    variants and presenting with a novel inflammatory bowel disease (IBD) phenotype that responded remarkably to thalidomide. We performed functional studies to reveal the pathogenicity of the\n                    <jats:italic>CSF3R<\/jats:italic>\n                    and to elucidate the potential mechanisms underlying the therapeutic effects of thalidomide. A comprehensive review of the literature identified 18 reported cases of SCN associated with\n                    <jats:italic>CSF3R<\/jats:italic>\n                    variants. We subsequently validated the pathogenicity of the variants in the patient\u2019s peripheral blood by flow cytometry, which demonstrated reduced granulocyte colony\u2010stimulating factor (G\u2010CSF) receptor (G\u2010CSFR) expression and markedly decreased phosphorylation of signal transducer and activator of transcription (STAT)3 (p\u2010STAT3) following stimulation with recombinant human G\u2010CSF (rhG\u2010CSF). Thalidomide augmented rhG\u2010CSF\u2010induced STAT3 phosphorylation in HEK293T cells harboring the\n                    <jats:italic>CSF3R Q257<\/jats:italic>\n                    <jats:italic>\u2009<\/jats:italic>\n                    <jats:sup>\u2217<\/jats:sup>\n                    or\n                    <jats:italic>R308G\/Q257<\/jats:italic>\n                    <jats:italic>\u2009<\/jats:italic>\n                    <jats:sup>\u2217<\/jats:sup>\n                    variants, and this effect was suppressed by a Janus kinase (JAK)1 inhibitor. Thus, IBD might represent a novel phenotype of SCN caused by\n                    <jats:italic>CSF3R<\/jats:italic>\n                    variants, and thalidomide could potentially alleviate the symptoms by modulating the JAK1\/STAT3 signaling pathway.\n                  <\/jats:p>","DOI":"10.1155\/jimr\/8163275","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:19:37Z","timestamp":1784701177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Crohn\u2019s Disease Phenotype in a Patient With Severe Congenital Neutropenia Caused by\n                    <i>CSF3R<\/i>\n                    Variants: Exploring the Pathogenesis and Effects of Thalidomide Treatment"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5181-5289","authenticated-orcid":false,"given":"Yanqiu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1530-6542","authenticated-orcid":false,"given":"Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4775-1587","authenticated-orcid":false,"given":"Chun","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-3585","authenticated-orcid":false,"given":"Zhiheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3620-7177","authenticated-orcid":false,"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1911-7466","authenticated-orcid":false,"given":"Xiaoxia","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1465-6727","authenticated-orcid":false,"given":"Cuifang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-7220","authenticated-orcid":false,"given":"Ying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2023.108476"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.32"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.08.011"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.7.2369"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-02-004275"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-406116"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-535419"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30039"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17081"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-23-0295"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14939"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-242-1"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27923"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001258"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001359"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-07-661264"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.746159"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19054"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.2741\/2041"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.11.2399"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2021.101516"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-2062"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2012.10.002"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2025-2"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0631-y"},{"key":"e_1_2_14_26_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.11.014"},{"key":"e_1_2_14_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1026511"},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00337-5"},{"key":"e_1_2_14_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm5120118"},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00871-3"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91350-U"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13181"},{"key":"e_1_2_14_33_2","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2015.1027687"},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114927"},{"key":"e_1_2_14_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-007-0786-8"},{"key":"e_1_2_14_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.766586"},{"key":"e_1_2_14_37_2","doi-asserted-by":"publisher","DOI":"10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