A new role for interferon gamma in neural stem/precursor cell dysregulation

Abstract

BackgroundThe identification of factors that compromise neurogenesis is aimed at improving stem cell-based approaches in the field of regenerative medicine. Interferon gamma (IFNγ) is a main pro-inflammatory cytokine and up-regulated during several neurological diseases. IFNγ is generally thought to beneficially enhance neurogenesis from fetal or adult neural stem/precursor cells (NSPCs).ResultsWe now provide direct evidence to the contrary that IFNγ induces a dysfunctional stage in a substantial portion of NSPC-derived progeny in vitro characterized by simultaneous expression of glial fibrillary acid protein (GFAP) and neuronal markers, an abnormal gene expression and a functional phenotype neither typical for neurons nor for mature astrocytes. Dysfunctional development of NSPCs under the influence of IFNγ was finally demonstrated by applying the microelectrode array technology. IFNγ exposure of NSPCs during an initial 7-day proliferation period prevented the subsequent adequate differentiation and formation of functional neuronal networks.ConclusionsOur results show that immunocytochemical analyses of NSPC-derived progeny are not necessarily indicating the correct cellular phenotype specifically under inflammatory conditions and that simultaneous expression of neuronal and glial markers rather point to cellular dysregulation. We hypothesize that inhibiting the impact of IFNγ on NSPCs during neurological diseases might contribute to effective neurogenesis and regeneration.

Activated CD8+ T Lymphocytes Inhibit Neural Stem/Progenitor Cell Proliferation: Role of Interferon-Gamma

“…Previous studies have shown that murine NSCs express functional IFN-γ receptors [37]. We verified, using a quantitative RT-PCR, that IFN-γR1 was expressed in NSC from all passages of culture used in this study (Fig.…”

“…These effects are initiated by IFN-γ binding to its cognate receptor, which is widely expressed on NSCs and its derivative cells [37]. Data presented in the present study demonstrate that by blocking IFN-γ R1, either using a neutralizing antibody or IFN-γ R1 KO NSCs, effectively abrogates the inhibitory effects produced by activated CD8 lymphocytes, indicating that these effects are likely mediated through the IFN-γ receptor.…”

Temporal profile of M1 and M2 responses in the hippocampus following early 24 h of neurotrauma

“…Inflated inflammatory factors increase the access of lymphocytes in the brain [10,17] to contribute inflammation, such as cytotoxic T-cell derived IFNγ contributes neuronal degeneration [26,50,87], and cause systemic effects after TBI [8,53,92]. In contrast, IFNγ contributes in M2 response [23], which is also associated with the prolonged blood infiltrated cells in the CNS [11,45,47,90].…”

Alcohol and adult hippocampal neurogenesis: Promiscuous drug, wanton effects

“…Inflammation can affect various phases of adult neurogenesis. For example, pro-inflammatory cytokine interleukin 6 (IL-6), results in decreased proliferation (Vallieres et al, 2002); whereas other pro-inflammatory cytokines such as interferon-gamma (IFN-γ) can alter fate choices from neuronal to astrocytic (Walter et al, 2011). …”