JOURNAL ARTICLE

Interferon-gamma inhibits the neuronal differentiation of neural progenitor cells by inhibiting the expression of Neurogenin2 via the JAK/STAT1 pathway

Jyhyun Ahn, Junsub Lee, Sunyoung Kim
Biochemical and Biophysical Research Communications 2015 October 9, 466 (1): 52-9
26325468
Interferon-gamma (IFN-γ) is one of the critical cytokines released by host immune cells upon infection. Despite the important role(s) of IFN-γ in host immune responses, there has been no in vivo study regarding the effects of IFN-γ on brain development, and the results from many in vitro studies are controversial. In this study, the effects of IFN-γ on embryonic neurogenesis were investigated. Treatment of E14.5 mouse neural progenitor cells (NPCs) with IFN-γ resulted in a decrease in the percentage of TuJ1-positive immature neurons but an increase in the percentage of Nestin-positive NPCs. Similar results were obtained in vivo. Treatment of NPCs with a JAK inhibitor or the knockdown of STAT1 expression abrogated the IFN-γ-mediated inhibition of neurogenesis. Interestingly, the expression of one of proneural genes, Neurogenin2 (Neurog2) was dramatically inhibited upon IFN-γ treatment, and cells overexpressing Neurog2 did not respond to IFN-γ. Taken together, our results demonstrate that IFN-γ inhibits neuronal differentiation of NPCs by negatively regulating the expression of Neurog2 via the JAK/STAT1 pathway. Our findings may provide an insight into the role of IFN-γ in the development of embryonic brain.

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