{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:34:22Z","timestamp":1783103662875,"version":"3.54.6"},"reference-count":22,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"unspecified","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Hunan Provincial Natural Science of Foundation","award":["2020JJ5820"],"award-info":[{"award-number":["2020JJ5820"]}]},{"name":"Hunan Provincial Natural Science of Foundation","award":["2021JJ40861"],"award-info":[{"award-number":["2021JJ40861"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101285"],"award-info":[{"award-number":["82101285"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102284"],"award-info":[{"award-number":["82102284"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for the Central Universities of Central South University","doi-asserted-by":"crossref","award":["2021zzts1070"],"award-info":[{"award-number":["2021zzts1070"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["80271347"],"award-info":[{"award-number":["80271347"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2022,12,5]]},"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The overexpansion of CD3<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup> cells is the hallmark and main pathological mechanism of clinical manifestations of spontaneously developed MRL\/lpr mice, which are primarily used as a mouse model of SLE. Our recent report demonstrated that blocking brain-derived neurotrophic factor precursor (proBDNF) suppressed the antibody-secreting cell differentiation and proliferation and inhibited the progression of SLE; however, the effect of proBDNF blockade on these CD3<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup> cells in MRL\/lpr mice is unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To explore the effect of proBDNF on CD3<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup> cells, MRL\/lpr mice at 12 weeks old were intraperitoneally injected with monoclonal anti-proBDNF antibody (McAb-proB) or control IgG continuously for 8 weeks. The manifestations in mice were observed, and peripheral blood and splenocytes were collected and analysed via flow cytometry at 20 weeks old. In addition, splenic CD3<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup> cells were subjected to RNA sequencing (RNA-seq) analysis to identify transcriptomic alterations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CD3<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup> cells in peripheral blood (p=0.0101) and spleen (p&lt;0.0001) were expanded in MRL\/lpr mice. Meanwhile, inhibition of proBDNF signalling reduced the percentage of CD3<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup> cells in peripheral blood (p=0.0036) and spleen (p=0.0280), alleviated lymphadenopathy, reduced urine protein level (p&lt;0.0001) and increased the body weight (p=0.0493). RNA-seq revealed 501 upregulated and 206 downregulated genes in splenic CD3<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup> cells in McAb-proB-treated MRL\/lpr mice compared with IgG-treated mice. The differentially expressed genes were found to be involved in apoptosis, tumour necrosis factor signalling, and T cell differentiation and proliferation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Systemic blockade of proBDNF inhibited the overexpansion of CD3<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup> cells and altered their signals related to cell cycle, cell apoptosis and the immune response, which may contribute to the attenuation of disease symptoms in murine lupus.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/lupus-2022-000836","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T11:16:29Z","timestamp":1672312589000},"page":"e000836","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Systemic blockade of proBDNF inhibited the expansion and altered the transcriptomic expression in CD3<sup>+<\/sup>B220<sup>+<\/sup> cells in MRL\/lpr lupus mice"],"prefix":"10.1136","volume":"9","author":[{"given":"An-Hui","family":"Zha","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Yun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7218-0387","authenticated-orcid":false,"given":"Di","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Xiangya Hospital Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Ping","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"2025091513294166000_9.1.e000836.1","doi-asserted-by":"crossref","first-page":"ITC81","DOI":"10.7326\/AITC202006020","article-title":"Systemic lupus erythematosus","volume":"172","author":"Kiriakidou","year":"2020","journal-title":"Ann Intern 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