I型干扰素增强人类背部根结节受体的刺激性,并诱导TRPV1敏感性
Úrzula Franco-Enzástiga1, Keerthana Natarajan1, Felipe Espinosa1
1Department of Neuroscience, University of Texas at Dallas, Dallas, United States of America.
JCI insight
|September 2, 2025
概括
一类干扰素 (IFN) 激活人类的感觉神经元,导致疼痛. 使用eFT508抑制特定的激酶 (MNK1/ 2) 阻断了IFN诱导的神经过敏和疼痛敏感性.
科学领域:
- 神经科学
- 免疫学
- 疼痛研究
背景情况:
- I型干扰素 (IFN) 对于抗病毒防御至关重要,但与类风湿性关节炎,狼和神经病痛等痛苦疾病有关.
- 已知IFN-α治疗会引起疼痛症状,研究表明IFN直接影响感官神经元,尽管动物对其疼痛调节效应的数据是相互矛盾的.
研究的目的:
- 澄清IFN-α和IFN-β对人类背根结节 (hDRG) 恶感受体的特定作用.
- 研究I型IFN对人类感觉神经元的信号通路和电生理影响.
主要方法:
- 在hDRG神经元上分析IFN受体子单元表达 (IFNAR1,IFNAR2).
- 测量STAT1和MAPK信号通路的激活 (eIF4E酸化).
- 补丁电生理学,Ca2+成像和多电极阵列,以评估神经元刺激性和对素的反应.
主要成果:
- IFN受体子单元IFNAR1和IFNAR2在hDRG神经元上表达.
- IFN-α和IFN-β激活了STAT1和MAPK信号通路.
- 对IFN-α和-β的急性和长期暴露都会增加hDRG神经元的刺激性,并延长素诱导的反应.
- 使用eFT508抑制MNK1/ 2激酶阻断了素反应的延长.
结论:
- 在hDRG受体上与IFNAR1/ 2相互作用,诱导神经元过度兴奋.
- 通过MNK1/ 2激酶激活,IFN诱导TRPV1通道的敏感化.
- 这些发现提供了将I型IFN与疼痛发展联系起来的细胞机制.
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