MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

Carolina Cebrián, Fabio A. Zucca, Pierluigi Mauri, Julius A. Steinbeck, Lorenz Studer, Clemens R. Scherzer, Ellen Kanter, Sadna Budhu, Jonathan Mandelbaum, Jean P. Vonsattel, Luigi Zecca, John D. Loike and David Sulzer ()
Additional contact information
Carolina Cebrián: Columbia University Medical Center
Fabio A. Zucca: Institute of Biomedical Technologies, National Research Council of Italy
Pierluigi Mauri: Institute of Biomedical Technologies, National Research Council of Italy
Julius A. Steinbeck: Center for Stem Cell Biology, Sloan-Kettering Institute
Lorenz Studer: Center for Stem Cell Biology, Sloan-Kettering Institute
Clemens R. Scherzer: The Neurogenomics Laboratory, Harvard Medical School and Brigham and Women’s Hospital
Ellen Kanter: Columbia University Medical Center
Sadna Budhu: Sloan Kettering Memorial Hospital
Jonathan Mandelbaum: Discovery Oncology Biology, Takeda Pharmaceuticals International Co., 40 Landsdowne Street
Jean P. Vonsattel: New York Brain Bank, Columbia University Medical Center
Luigi Zecca: Institute of Biomedical Technologies, National Research Council of Italy
John D. Loike: Columbia University Medical Center
David Sulzer: Columbia University Medical Center

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract Subsets of rodent neurons are reported to express major histocompatibility complex class I (MHC-I), but such expression has not been reported in normal adult human neurons. Here we provide evidence from immunolabel, RNA expression and mass spectrometry analysis of postmortem samples that human catecholaminergic substantia nigra and locus coeruleus neurons express MHC-I, and that this molecule is inducible in human stem cell-derived dopamine (DA) neurons. Catecholamine murine cultured neurons are more responsive to induction of MHC-I by gamma-interferon than other neuronal populations. Neuronal MHC-I is also induced by factors released from microglia activated by neuromelanin or alpha-synuclein, or high cytosolic DA and/or oxidative stress. DA neurons internalize foreign ovalbumin and display antigen derived from this protein by MHC-I, which triggers DA neuronal death in the presence of appropriate cytotoxic T cells. Thus, neuronal MHC-I can trigger antigenic response, and catecholamine neurons may be particularly susceptible to T-cell-mediated cytotoxic attack.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms4633 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4633

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms4633

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().