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Lymphocyte activation gene 3 (Lag3) expression is increased in prion infections but does not modify disease progression


Liu, Yingjun; Sorce, Silvia; Nuvolone, Mario; Domange, Julie; Aguzzi, Adriano (2018). Lymphocyte activation gene 3 (Lag3) expression is increased in prion infections but does not modify disease progression. Scientific Reports, 8:14600.

Abstract

Prion diseases, Alzheimer’s disease and Parkinson’s disease (PD) are fatal degenerative disorders that share common neuropathological and biochemical features, including the aggregation of pathological protein conformers. Lymphocyte activation gene 3 (Lag3, also known as CD223) is a member of the immunoglobulin superfamily of receptors expressed on peripheral immune cells, microglia and neurons, which serves as a receptor for α-synuclein aggregates in PD. Here we examined the possible role of Lag3 in the pathogenesis of prion diseases. Through quantitative real-time PCR and RNA-sequencing, we found that the expression levels of Lag3 were relatively low in the adult mouse brains, yet its expression was increased after prion infection. However, we failed finding significant differences regarding the incubation time, PrPSc load, neurodegeneration, astrocyte and microglia reactions and inflammatory gene expression between the Lag3 knockout mice and wild-type littermate controls after prion infection. We conclude that loss of Lag3 has no significant influence on prion disease pathogenesis. Considering that Lag3 is an immune checkpoint receptor, our results suggest that immune checkpoint inhibition (an increasingly prevalent therapeutic modality against many types of cancer) might not exert positive or negative effects on the progression of prion diseases.

Abstract

Prion diseases, Alzheimer’s disease and Parkinson’s disease (PD) are fatal degenerative disorders that share common neuropathological and biochemical features, including the aggregation of pathological protein conformers. Lymphocyte activation gene 3 (Lag3, also known as CD223) is a member of the immunoglobulin superfamily of receptors expressed on peripheral immune cells, microglia and neurons, which serves as a receptor for α-synuclein aggregates in PD. Here we examined the possible role of Lag3 in the pathogenesis of prion diseases. Through quantitative real-time PCR and RNA-sequencing, we found that the expression levels of Lag3 were relatively low in the adult mouse brains, yet its expression was increased after prion infection. However, we failed finding significant differences regarding the incubation time, PrPSc load, neurodegeneration, astrocyte and microglia reactions and inflammatory gene expression between the Lag3 knockout mice and wild-type littermate controls after prion infection. We conclude that loss of Lag3 has no significant influence on prion disease pathogenesis. Considering that Lag3 is an immune checkpoint receptor, our results suggest that immune checkpoint inhibition (an increasingly prevalent therapeutic modality against many types of cancer) might not exert positive or negative effects on the progression of prion diseases.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Multidisciplinary
Language:English
Date:1 December 2018
Deposited On:25 Oct 2018 12:32
Last Modified:01 Nov 2018 01:15
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41598-018-32712-8
PubMed ID:30279468
Project Information:
  • : FunderFP7
  • : Grant ID250356
  • : Project TitleThe prion protein in health and disease
  • : FunderSNSF
  • : Grant ID310030B_160329
  • : Project TitleThe prion protein in health and disease
  • : FunderSNSF
  • : Grant IDCRSII3_147660
  • : Project TitleCalcium imaging of cellular and circuit dysfunctions in neurodegeneration
  • : FunderSystemsX.ch
  • : Grant ID2014/260
  • : Project TitlePrionX
  • : FunderSystemsX.ch
  • : Grant ID2015/320
  • : Project TitleSynucleiX
  • : FunderCRPP
  • : Grant ID
  • : Project TitleSmallRNAs
  • : FunderCRPP
  • : Grant ID
  • : Project TitleHuman Hemato-Lymphatic Diseases

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