{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:51:17Z","timestamp":1791978677779,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","award":["ARUK\u20102020DDI\u2010OX"],"award-info":[{"award-number":["ARUK\u20102020DDI\u2010OX"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"abstract":"<jats:p>\n                    Genetic and functional studies strongly implicate microglia in the pathology of Alzheimer's disease. The Triggering Receptor Expressed on Myeloid cells 2 (TREM2) pathway is an important functional regulator of microglia, promoting phagocytosis of apoptotic cells, debris and pathogenic proteins. Genome\u2010wide association studies have identified risk\u2010bearing polymorphisms in several members of the pathway including\n                    <jats:italic>INPP5D,<\/jats:italic>\n                    encoding the inositol phosphatase SHIP1. Recent studies utilising\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    disease\u2010relevant models have identified a role for SHIP1 in modulating TREM2 signalling and neurotoxic microglial activation. In this study, we characterised the role of SHIP1 in regulating TREM2 signalling and myeloid functions using human\u2010induced pluripotent stem cell (hiPSC)\u2010derived macrophages. Characterisation of isogenic SHIP1 knockout (SHIP1 KO) macrophages showed decreased expression of the lipopolysaccharide (LPS) coreceptor CD14, which translated to lower secretion of pro\u2010inflammatory cytokines. Additionally, loss of SHIP1 in this macrophage model attenuated TREM2 signalling, which was further reflected in a reduced level of phagocytosis of apoptotic neurons compared to the parental line. The observed effects on TREM2 signalling did not correspond to changes in total protein levels or shedding. Further examination of macrophage scavenger receptor expression revealed reduced cell surface levels of CD163 and CD206 involved in resolution of inflammation, but increased levels of the phagocytic receptor MerTK. Morphological analysis revealed a less amoeboid\u2010activated phenotype and increased adhesion in the SHIP1 KO macrophages. Taken together, our data indicate that SHIP1 plays a key role in modulating TREM2 signalling, inflammation and phagocytosis.\n                  <\/jats:p>","DOI":"10.1111\/febs.70752","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:15:07Z","timestamp":1791976507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>SHIP1<\/scp>\n                    regulates\n                    <scp>TREM2<\/scp>\n                    signalling and macrophage functions in a\n                    <scp>hiPSC<\/scp>\n                    \u2010derived model"],"prefix":"10.1111","author":[{"given":"Kim S.","family":"Martin","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine Research Building Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Obst","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Research Building Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shania","family":"Ibarra","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Research Building Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Research Building Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-0460","authenticated-orcid":false,"given":"Katerina O.","family":"Gospodinova","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Research Building Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Mead","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Research Building Alzheimer's Research UK Oxford Drug Discovery Institute, University of Oxford  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s40120-022-00338-8","article-title":"Alzheimer's disease: epidemiology and clinical progression","volume":"11","author":"Monfared A","year":"2022","journal-title":"Neurol Ther"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-017-0184-x","article-title":"Late onset Alzheimer's 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