Cell type‐specific regulation of major histocompatibility complex (MHC) Class I gene expression in astrocytes, oligodendrocytes, and neurons

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Abstract
Mechanisms of major histocompatibility complex (MHC) class I gene regulation in cells of the CNS have been studied in vitro. Astrocytes in primary cultures, but neither oligodendrocytes nor neurons, constitutively expressed cell surface MHC class I molecules. Interferon-gamma (IFN-γ) treatment led to induction of MHC class I expression in astrocytes and oligodendrocytes but not in neurons. The conserved up-stream sequence containing the juxtaposed nuclear factor (NF)-kB-like region I and IFN-response consensus sequence (ICS) constitutively enhanced MHC class I gene promoter activity in astrocytes, but not in oligodendrocytes or in neurons. Nuclear extracts from astrocytes, but not from oligodendrocytes and neurons, had a binding activity specific for the NF-kB-like region I sequence, indicating that constitutive expression of MHC class I genes is governed by the upstream region I enhancer and its binding factor. IFN-γ treatment led to induction of MHC class I promoter activity in astrocytes and oligodendrocytes, but not in neurons. In accordance with this observation, a nuclear factor that binds to the ICS was induced in astrocytes and oligodendrocytes but not in neurons following IFN-γ treatment. This study illustrates cell type-specific regulation of MHC class I genes in the CNS that correlates with the expression of DNA binding factors relevant to MHC class I gene transcription.