{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:43:32Z","timestamp":1780465412473,"version":"3.54.1"},"reference-count":65,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2024,6,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Parkinson\u2019s disease (PD) is characterized by alpha-synuclein ( \u03b1-Syn) pathology, neurodegeneration and neuroinflammation. Human leukocyte antigen ( HLA) variants associated with PD and \u03b1-Syn specific CD4+ T lymphocytes in PD patients highlight the importance of antigen presentation in PD etiology. The class II transactivator (CIITA) regulates major histocompatibility complex class II (MHCII) expression. Reduced Ciita levels significantly increase \u03b1-Syn pathology, nigrostriatal neurodegeneration and behavioral deficits in \u03b1-Syn-induced rat PD models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Characterize immune profiles associated with enhanced PD-like pathology observed in rats expressing lower Ciita levels (DA.VRA4) compared to the background strain (DA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>To model PD, we combined rAAV-mediated \u03b1-Syn overexpression in the substantia nigra with striatal injection of \u03b1-Syn preformed fibrils. Immune profiles in brain and blood were analyzed by flow cytometry and multiplexed ELISA in na\u00efve rats, 4- and 8 weeks post rAAV injection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Flow cytometry showed Ciita-dependent regulation of MHCII on microglia, brain macrophages and circulating myeloid cells. The MHCII-dependent microglial response was highest at 4 weeks post rAAV injection, whereas the MHCII levels in circulating myeloid cells was highest at 8 weeks. There was no major infiltration of macrophages or T lymphocytes into the CNS in response to \u03b1-Syn and only subtle Ciita- and\/or \u03b1-Syn-dependent changes in the T lymphocyte compartment. Lower Ciita levels were consistently associated with higher TNF levels in serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Ciita regulates susceptibility to PD-like pathology through minor but detectable changes in resident and peripheral immune cells and TNF levels, indicating that mild immunomodulatory therapies could have therapeutic effects in PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jpd-240062","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T11:43:23Z","timestamp":1715341403000},"page":"693-711","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>Ciita<\/i>\n                    Regulates Local and Systemic Immune Responses in a Combined rAAV-\n                    <i>\u03b1<\/i>\n                    -synuclein and Preformed Fibril-Induced Rat Model for Parkinson\u2019s Disease"],"prefix":"10.1177","volume":"14","author":[{"given":"Filip","family":"Fredlund","sequence":"first","affiliation":[{"name":"Department of Experimental Medical Science, Translational Neurogenetics Unit, Lund University, Lund, Sweden"},{"name":"Department of Clinical Sciences, Inflammation and Stem Cell Therapy Group, Division of Clinical Neurophysiology, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzia","family":"Jimenez-Ferrer","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Translational Neurogenetics Unit, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Grabert","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lautaro Francisco","family":"Belfiori","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Translational Neurogenetics Unit, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin","family":"Luk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Swanberg","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Translational Neurogenetics Unit, Lund University, Lund, 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