MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration Journal Article
| Authors: | Cebrián, C.; Zucca, F. A.; Mauri, P.; Steinbeck, J. A.; Studer, L.; Scherzer, C. R.; Kanter, E.; Budhu, S.; Mandelbaum, J.; Vonsattel, J. P.; Zecca, L.; Loike, J. D.; Sulzer, D. |
| Article Title: | MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration |
| 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. © 2014 Macmillan Publishers Limited. |
| Keywords: | adult; controlled study; human tissue; aged; human cell; nonhuman; antigen expression; mouse; cell death; gene expression; animal experiment; protein; antigen; gamma interferon; brain; public health; nucleotide sequence; cytotoxic t lymphocyte; locus ceruleus; oxidative stress; rodent; major histocompatibility complex; catecholamine; dopamine; dopaminergic nerve cell; neurology; major histocompatibility antigen class 1; nerve degeneration; microglia; ovalbumin; substantia nigra; human; male; female; article; alpha synuclein; neuromelanin; catecholamine nerve cell |
| Journal Title: | Nature Communications |
| Volume: | 5 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-04-16 |
| Start Page: | 3633 |
| Language: | English |
| DOI: | 10.1038/ncomms4633 |
| PROVIDER: | scopus |
| PMCID: | PMC4024461 |
| PUBMED: | 24736453 |
| DOI/URL: | |
| Notes: | Nat. Commun. -- Export Date: 2 June 2014 -- Molecular Sequence Numbers: GENBANK: AB257503, AJ276069, AJ429615, AM072964, AM746482, AM778129, AM905047, AM906166, AY918166, BC008457, BX248310, BX927178, CR388220, CR388229, CR759828, DQ238865, EF521874, EU580147, FJ222559, FJ618920, FN806794, HQ589100, X61703, X89707, X94571, Y14582; -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work