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We therefore hypothesized that decreased MHCII may mitigate dopaminergic degeneration. During an ongoing \u03b1-synuclein lesion, mice with MHCII reduction in systemic and brain innate immune cells (LysMCre\u2009+\u2009I-Ab\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    or CRE+) displayed brain T cell repertoire shifts and greater preservation of the dopaminergic phenotype in nigrostriatal terminals. Next, we investigated a human cohort to characterize the immunophenotype of subjects with and without the high-risk\n                    <jats:italic>GG<\/jats:italic>\n                    genotype at the\n                    <jats:italic>rs3129882<\/jats:italic>\n                    SNP. We confirmed that the high-risk\n                    <jats:italic>GG<\/jats:italic>\n                    genotype is associated with peripheral changes in MHCII inducibility, frequency of CD4\u2009+\u2009T cells, and differentially accessible chromatin regions within the MHCII locus. Although our mouse studies indicate that myeloid MHCII reduction coinciding with an intact adaptive immune system is insufficient to fully protect dopamine neurons from \u03b1-synuclein-induced degeneration, our data are consistent with the overwhelming evidence implicating antigen presentation in PD pathophysiology.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-95679-3","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T04:21:26Z","timestamp":1745209286000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MHCII reduction is insufficient to protect mice from alpha-synuclein-induced degeneration and the Parkinson\u2019s HLA locus exhibits epigenetic regulation"],"prefix":"10.1038","volume":"15","author":[{"given":"Elizabeth M.","family":"Kline","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janna E.","family":"Jernigan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher D.","family":"Scharer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakeenah L.","family":"Hicks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary K.","family":"Herrick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca L.","family":"Wallings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean D.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly B.","family":"Menees","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredric P.","family":"Manfredsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaus R.","family":"McFarland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy M.","family":"Boss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mal\u00fa G\u00e1mez","family":"Tansey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Joers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"95679_CR1","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.expneurol.2012.06.025","volume":"237","author":"MB Watson","year":"2012","unstructured":"Watson, M. 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