{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:01:27Z","timestamp":1790845287571,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070954"],"award-info":[{"award-number":["32070954"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neuroimmune responses critically shape the progression and outcome of ischemic stroke, yet the cell type\u2013specific roles of myeloid populations remain incompletely defined. Cathepsin B (CatB), a lysosomal cysteine protease, has been implicated in neuroinflammation, but its contribution from distinct myeloid subsets is unclear. Transient middle cerebral artery occlusion (tMCAO) was induced in wild\u2010type and CatB\u2010deficient mice. Bone marrow chimeras were generated to selectively delete CatB in peripheral myeloid cells or resident microglia. Infarct severity, mortality, myeloid phenotypes, and transcriptional programs were assessed using flow cytometry, immunofluorescence, and bulk and cell type\u2013resolved RNA sequencing. CatB expression was markedly upregulated in ischemic brain myeloid cells, with higher levels in infiltrating macrophages than in microglia. Selective deletion of CatB in peripheral myeloid cells, but not in microglia, significantly reduced infarct size, mortality, and pro\u2010inflammatory gene expression after tMCAO. Transcriptomic analyses showed suppression of inflammatory pathways and preservation of neuronal signaling in mice lacking macrophage\u2010derived CatB. Cell type\u2013resolved RNA sequencing revealed that CatB deficiency shifted infiltrating macrophages toward a pro\u2010resolving, tissue\u2010repair phenotype characterized by increased expression of M2\u2010associated genes, including Chil3. Consistently, CatB\u2010deficient macrophages displayed enhanced pro\u2010resolving polarization in response to ischemic neuron\u2013derived signals in\u00a0vitro. CatB was also elevated in circulating Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    monocytes after stroke. These findings identify peripheral myeloid\u2013derived CatB as a key driver of ischemic brain injury and a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/glia.70228","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:33:43Z","timestamp":1790843623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage\u2010Derived, Rather Than Microglial, Cathepsin B Exacerbates Brain Injury After Ischemic Stroke"],"prefix":"10.1002","volume":"74","author":[{"given":"Wei","family":"Kong","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science Beijing Institute of Technology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biology Shenzhen MSU\u2010BIT University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-9037","authenticated-orcid":false,"given":"Zhou","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Aging Science and Pharmacology, Faculty of Dental Science Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7750-0674","authenticated-orcid":false,"given":"Yoshinori","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Physiology Nihon University School of Dentistry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2610-3203","authenticated-orcid":false,"given":"Hiroshi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy Yasuda Women's University  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology Aerospace Central Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9860-1511","authenticated-orcid":false,"given":"Yutong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Aerospace Central Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2820-450X","authenticated-orcid":false,"given":"Hong","family":"Qing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science Beijing Institute of Technology  Beijing China"},{"name":"Department of Biology Shenzhen MSU\u2010BIT University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-0371","authenticated-orcid":false,"given":"Zhenzhen","family":"Quan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science Beijing Institute of Technology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8486-8146","authenticated-orcid":false,"given":"Junjun","family":"Ni","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science Beijing Institute of Technology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"e_1_2_14_2_1","first-page":"S18","article-title":"Infiltrating Monocytes Trigger EAE Progression but Fail to Contribute to the Resident Microglia Pool","volume":"17","author":"Ajami B.","year":"2011","journal-title":"Multiple Sclerosis Journal"},{"key":"e_1_2_14_3_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrneurol.2012.98","article-title":"The Immunology of Acute Stroke","volume":"8","author":"Chamorro A.","year":"2012","journal-title":"Nature Reviews Neurology"},{"key":"e_1_2_14_4_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s11481-016-9721-6","article-title":"Cathepsin B Improves ss\u2010Amyloidosis and Learning and Memory in Models of Alzheimer's Disease","volume":"12","author":"Embury C. 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