Interferon-gamma(IFN-γ) is critical for central nervous system(CNS) functions and it may be a promising treatment to stimulate CNS regeneration. However, previous studies reported inconsistent results, and the molecular mechanisms remain controversial. Here we show that IFN-γ-treated mice via intraperitoneal injection have elevated IFN-γ level in central hippocampus and superior cognitive behaviors IFN-γ could activates the level of protein expression of Wnt7a, β-catenin, and CyclinD1 in Wnt/β-catenin signaling pathway of mice hippocampus. Functional and mechanism analysis in vitro revealed that IFN-γ promoted the proliferation and differentiation in primary cultured neural stem cells(NSCs). STAT1 was accountable for IFN-γ-induced activation of the β-catenin promoter, and IFN-γ increased the binding affinity of STAT1 to β-catenin promoter based on luciferase activity and chromatin immunoprecipitation. Our results suggest that IFN-γ exerts many effects ranging from cognitive function in vivo to NSC proliferation, self-renewal, and differentiation in vitro. It does so by recruiting STAT1 to the β-catenin promoter, enhancing cis-regulation by STAT1, and ultimately activating Wnt/β-catenin signaling. In this study, we first found that STAT1 was recruited into the promoter of β-catenin to activate β-catenin expression, and this effect was regulated by IFN-γ. It is also discovered firstly that Wnt/β-catenin and JAK/STAT pathways form cross-links through STAT1. Promoting neurogenesis through immune stimulation might be a promising strategy for repairing the diseased/injured CNS. This study provides a scientific basis for immunomodulation to promote nerve regeneration and offer a new therapeutic direction for central nervous system regeneration.

干扰素-γ（IFN-γ）对中枢神经系统（CNS）功能至关重要，它可能是刺激CNS再生的有希望的治疗方法。然而，先前的研究报告的结果不一致，分子机制仍存在争议。在这里，我们表明通过腹腔注射 IFN-γ 治疗的小鼠在中央海马中的 IFN-γ 水平升高，并且具有优越的认知行为 IFN-γ 可以激活 Wnt/β- 中 Wnt7a、β-catenin 和 CyclinD1 的蛋白质表达水平。小鼠海马连环蛋白信号通路。体外功能和机制分析表明，IFN-γ促进原代培养的神经干细胞（NSCs）的增殖和分化。STAT1 负责 IFN-γ 诱导的 β-catenin 启动子激活，基于荧光素酶活性和染色质免疫沉淀，IFN-γ 增加了 STAT1 与 β-catenin 启动子的结合亲和力。我们的研究结果表明，IFN-γ 发挥许多作用，从体内的认知功能到体外的 NSC 增殖、自我更新和分化。它通过将 STAT1 募集到 β-catenin 启动子，增强 STAT1 的顺式调节，并最终激活 Wnt/β-catenin 信号传导来实现。在这项研究中，我们首先发现 STAT1 被募集到 β-catenin 的启动子中以激活 β-catenin 的表达，并且这种作用受 IFN-γ 的调节。还首次发现Wnt/β-catenin和JAK/STAT通路通过STAT1形成交联。通过免疫刺激促进神经发生可能是修复患病/受伤中枢神经系统的一种有前途的策略。