Context matters: Conflicting roles of interferon-γ signaling in CNS diseases

IF 5.6 2区医学 Q1 NEUROSCIENCES

Current Opinion in Neurobiology Pub Date : 2026-02-01 Epub Date: 2025-12-16 DOI:10.1016/j.conb.2025.103149

Jonathan Nulman , Jason D. Ulrich , David M. Holtzman

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Abstract

Interferon-gamma (IFNγ) is a pleiotropic cytokine produced by CD8+ and CD4+ Th1 T cells, natural killer cells, natural killer-T cells, and type 1 innate lymphoid cells. Canonical IFNγ-induced genes include cytokines, chemokines, antigen processing and presentation machinery, and other transcription factors that initiate secondary, cell type-specific IFNγ responses. Originally described as an antiviral molecule, additional roles for IFNγ in development, anti-infection immunity, and neurodegeneration have been described. However, IFNγ′s downstream effects are highly context-dependent. Recent studies have uncovered extensive neuroimmune interactions within the CNS and implicated IFNγ in numerous CNS diseases, although these studies have produced conflicting results. This highlights a need for functional studies accounting for the spatial, temporal, and cellular complexities of CNS IFNγ signaling. Here, we summarize the current understanding of IFNγ signaling in CNS infections, multiple sclerosis/experimental autoimmune encephalomyelitis, and aging-associated neurodegenerative diseases and propose a framework for the design of future studies investigating the role of CNS IFNγ signaling.

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背景问题：干扰素-γ信号在中枢神经系统疾病中的相互冲突的作用。

干扰素γ (IFNγ)是一种由CD8+和CD4+ Th1 T细胞、自然杀伤细胞、自然杀伤T细胞和1型先天淋巴样细胞产生的多效细胞因子。典型的IFNγ诱导基因包括细胞因子、趋化因子、抗原加工和呈递机制，以及其他启动次级、细胞类型特异性IFNγ反应的转录因子。最初被描述为抗病毒分子，IFNγ在发育，抗感染免疫和神经退行性变中的其他作用已经被描述。然而，IFNγ的下游效应是高度依赖于环境的。最近的研究发现了中枢神经系统内广泛的神经免疫相互作用，并暗示IFNγ与许多中枢神经系统疾病有关，尽管这些研究产生了相互矛盾的结果。这强调了对CNS IFNγ信号的空间、时间和细胞复杂性进行功能研究的必要性。在这里，我们总结了IFNγ信号在中枢神经系统感染、多发性硬化症/实验性自身免疫性脑脊髓炎和衰老相关神经退行性疾病中的当前理解，并提出了一个框架，用于设计未来研究中枢神经系统IFNγ信号的作用。

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来源期刊

Current Opinion in Neurobiology 医学-神经科学

CiteScore

11.10

自引率

1.80%

发文量

130

审稿时长

4-8 weeks

期刊介绍： Current Opinion in Neurobiology publishes short annotated reviews by leading experts on recent developments in the field of neurobiology. These experts write short reviews describing recent discoveries in this field (in the past 2-5 years), as well as highlighting select individual papers of particular significance. The journal is thus an important resource allowing researchers and educators to quickly gain an overview and rich understanding of complex and current issues in the field of Neurobiology. The journal takes a unique and valuable approach in focusing each special issue around a topic of scientific and/or societal interest, and then bringing together leading international experts studying that topic, embracing diverse methodologies and perspectives. Journal Content: The journal consists of 6 issues per year, covering 8 recurring topics every other year in the following categories: -Neurobiology of Disease- Neurobiology of Behavior- Cellular Neuroscience- Systems Neuroscience- Developmental Neuroscience- Neurobiology of Learning and Plasticity- Molecular Neuroscience- Computational Neuroscience