Differential expression of interferon-γ receptor on human glial cells in vivo and in vitro

Abstract 

Although significant effects of interferon-γ (IFN-γ) on glial cells are well documented, information on the expression level and localization of glial IFN-γ receptors (IFN-γ-R) in the human central nervous system (CNS) is sparse. To examine the glial expression of IFN-γ-R in the human CNS, immunohistochemistry and quantitative analyses were performed on Alzheimer disease hippocampus, Parkinson disease substantia nigra, amyotrophic lateral sclerosis spinal cord and corresponding areas from non-neurological cases. Almost all IFN-γ-R-positive (IFN-γ-R⁺) cells corresponded to GFAP-positive (GFAP⁺) astrocytes, while none of IFN-γ-R⁺ cells corresponded to IBA1-positive (IBA1⁺) microglia or MBP-positive (MBP⁺) oligodendrocytes in these neurological cases. We observed a similar pattern of glial IFN-γ-R expression in non-neurological cases. Also, we quantitatively analyzed the IFN-γ-R expression by cultured human glial cells using immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). In contrast to in vivo results, almost all IFN-γ-R⁺ cells were IBA1⁺ in microglial cultures, GFAP⁺ in astrocytic cultures and MBP⁺ in oligodendrocytic cultures. Moreover, no significant difference in IFN-γ-R mRNA expression was found for these glial cell types by RT-PCR. These results suggest that the microglial and oligodendrocytic expression levels of IFN-γ-R are much lower than the astrocytic expression levels in the human CNS in vivo, whereas all three types of glial cells constitutively express IFN-γ-R when cultured in vitro.

Keywords: Interferon-γ receptor, Microglia, Astrocytes, Oligodendrocytes, Neurodegenerative diseases