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Over the past decade, the importance of microglia in brain development, particularly in synaptic elimination, has become evident. Thus, microglial abnormalities may lead to synaptic dysfunction, which may underlie the pathogenesis of ASD. Several human studies have demonstrated aberrant microglial activation in the brains of individuals with ASD, and studies in animal models of ASD have also shown a relationship between microglial dysfunction and synaptic abnormalities. However, there are very few methods available to directly assess whether phagocytosis by human microglia is abnormal. Microglia are tissue-resident macrophages with phenotypic similarities to monocyte-derived macrophages, both of which consistently exhibit pathological phenotypes in individuals with ASD. Therefore, in this study, we examined the phagocytosis capacity of human macrophages derived from peripheral blood monocytes. These macrophages were polarized into two types: those induced by granulocyte-macrophage colony-stimulating factor (GM-CSF M\u03a6, traditionally referred to as \u201cM1 M\u03a6\u201d) and those induced by macrophage colony-stimulating factor (M-CSF M\u03a6, traditionally referred to as \u201cM2 M\u03a6\u201d). Synaptosomes purified from human induced pluripotent stem cell-derived neuron were used to assess phagocytosis capacity. Our results revealed that M-CSF M\u03a6 exhibited higher phagocytosis capacity compared to GM-CSF M\u03a6, whereas ASD-M-CSF M\u03a6 showed a marked impairment in phagocytosis. Additionally, we found a positive correlation between phagocytosis capacity and\n                    <jats:italic>cluster of differentiation 209<\/jats:italic>\n                    expression. This research contributes to a deeper understanding of the pathobiology of ASD and offers new insights into potential therapeutic targets for the disorder.\n                  <\/jats:p>","DOI":"10.1038\/s41380-025-03002-3","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:23:01Z","timestamp":1743812581000},"page":"3837-3845","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impaired synaptosome phagocytosis in macrophages of individuals with autism spectrum disorder"],"prefix":"10.1038","volume":"30","author":[{"given":"Yuki","family":"Nishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-4173","authenticated-orcid":false,"given":"Michihiro","family":"Toritsuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryohei","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rio","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Kayashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahira","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-7049","authenticated-orcid":false,"given":"Kazuki","family":"Okumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4362-3262","authenticated-orcid":false,"given":"Kazuhiko","family":"Yamamuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minobu","family":"Ikehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Noriyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Kamikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Murayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4109-7657","authenticated-orcid":false,"given":"Hidetaka","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-5935","authenticated-orcid":false,"given":"Hideyuki","family":"Okano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3189-6076","authenticated-orcid":false,"given":"Nakao","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Makinodan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"3002_CR1","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1111\/pcn.12860","volume":"73","author":"S Gyawali","year":"2019","unstructured":"Gyawali S, Patra BN. 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