Format

Send to

Choose Destination
Sci Rep. 2018 Oct 2;8(1):14600. doi: 10.1038/s41598-018-32712-8.

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

Author information

1
Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland. yingjun.liu@usz.ch.
2
Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland.
3
Amyloidosis Research and Treatment Center, Foundation Scientific Institute Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Pavia, Italy.
4
Institute of Neuropathology, University of Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland. adriano.aguzzi@usz.ch.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center