Evidence map›Paper›PMID 38728204›Full record

ArticleJournal of Parkinson's disease2024

Ciita Regulates Local and Systemic Immune Responses in a Combined rAAV-α-synuclein and Preformed Fibril-Induced Rat Model for Parkinson's Disease.

Filip Fredlund, Itzia Jimenez-Ferrer, Kathleen Grabert, Lautaro Francisco Belfiori, Kelvin Luk, Maria Swanberg

Abstract read
In one paragraph

Article in Journal of Parkinson's disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Filip FredlundDepartment of Experimental Medical Science, Translational Neurogenetics Unit, Lund University, Lund, Sweden.
Itzia Jimenez-FerrerDepartment of Experimental Medical Science, Translational Neurogenetics Unit, Lund University, Lund, Sweden.
Kathleen GrabertInstitute of Environmental Medicine, Toxicology Unit, Karolinska Institutet, Stockholm, Sweden.
Lautaro Francisco BelfioriDepartment of Experimental Medical Science, Translational Neurogenetics Unit, Lund University, Lund, Sweden.
Kelvin LukDepartment of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Maria SwanbergDepartment of Experimental Medical Science, Translational Neurogenetics Unit, Lund University, Lund, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Parkinson's disease (PD) is characterized by alpha-synuclein (α-Syn) pathology, neurodegeneration and neuroinflammation. Human leukocyte antigen (HLA) variants associated with PD and α-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 α-Syn pathology, nigrostriatal neurodegeneration and behavioral deficits in α-Syn-induced rat PD models. Objective: Characterize immune profiles associated with enhanced PD-like pathology observed in rats expressing lower Ciita levels (DA.VRA4) compared to the background strain (DA). Methods: To model PD, we combined rAAV-mediated α-Syn overexpression in the substantia nigra with striatal injection of α-Syn preformed fibrils. Immune profiles in brain and blood were analyzed by flow cytometry and multiplexed ELISA in naïve rats, 4- and 8 weeks post rAAV injection. Results: 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 α-Syn and only subtle Ciita- and/or α-Syn-dependent changes in the T lymphocyte compartment. Lower Ciita levels were consistently associated with higher TNF levels in serum. Conclusions: 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.

Indexed as

alpha-SynucleinDisease Models, AnimalParkinson DiseaseTrans-ActivatorsAnimalsDependovirusMicrogliaNuclear ProteinsRatsSubstantia Nigraalpha-SynucleinMHC class II transactivator proteinNuclear ProteinsTrans-Activatorsalpha-synucleinMHC class II genesMHC class II transactivator proteinneuroinflammationParkinson’s diseasetumor necrosis factor

Identifiers

PMID38728204
PMCPMC11191526

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.