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Yet, the impact of this protective mutation on microglial responses to AD pathology remains unknown. Chimeric AD and wild\u2010type mice were generated by transplanting PLCG2\u2010P522R or isogenic wild\u2010type human induced pluripotent stem cell microglia. At 7 months of age, single\u2010cell and bulk RNA sequencing, and histological analyses were performed. The PLCG2\u2010P522R variant induced a significant increase in microglial human leukocyte antigen (HLA) expression and the induction of antigen presentation, chemokine signaling, and T cell proliferation pathways. Examination of immune\u2010intact AD mice further demonstrated that the PLCG2\u2010P522R variant promotes the recruitment of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells to the brain. These data provide the first evidence that the PLCG2\u2010P522R variant increases the capacity of microglia to recruit T cells and present antigens, promoting a microglial transcriptional state that has recently been shown to be reduced in AD patient brains.\n                  <\/jats:p>","DOI":"10.1002\/alz.12577","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T01:18:02Z","timestamp":1644455882000},"page":"1765-1778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7765-0445","authenticated-orcid":false,"given":"Christel","family":"Claes","sequence":"first","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California Irvine  Irvine California USA"},{"name":"Sue and Bill Gross Stem Cell Research Center University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney E.","family":"England","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma P.","family":"Danhash","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California Irvine  Irvine California USA"},{"name":"Sue and Bill Gross Stem Cell Research Center University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Kiani Shabestari","sequence":"additional","affiliation":[{"name":"Sue and Bill Gross Stem Cell Research Center University of California Irvine  Irvine California USA"},{"name":"Department of Neurobiology and Behavior University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Jairaman","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Paul","family":"Chadarevian","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California Irvine  Irvine California USA"},{"name":"Sue and Bill Gross Stem Cell Research Center University of California Irvine  Irvine California USA"},{"name":"Department of Neurobiology and Behavior University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Hasselmann","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California Irvine  Irvine California USA"},{"name":"Sue and Bill Gross Stem Cell Research Center University of California Irvine  Irvine California USA"},{"name":"Department of Neurobiology and Behavior University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy P.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute IUSM  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan A.","family":"Coburn","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tau En","family":"Lim","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge L. 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