Interferon-β Intensifies Interleukin-23-Driven Pathogenicity of T Helper Cells in Neuroinflammatory Disease.
Interferon-β Intensifies Interleukin-23-Driven Pathogenicity of T Helper Cells in Neuroinflammatory Disease.
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β干扰素增强了神经炎症性疾病中白细胞介素 - 23驱动的辅助性T细胞的致病性。
DOI：
10.3390/cells10082139
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发表时间：
2021-08-20
期刊：
影响因子：
6
通讯作者：
Axtell RC
中科院分区：
文献类型：
--
作者：
Agasing A;Quinn JL;Kumar G;Axtell RC
干扰素（IFN）-β是多发性硬化（MS）的常用疗法。然而，25-40%的患者对这种疗法无反应，这是另一种神经炎性疾病-视神经肌萎缩症（NMO）。我们先前在NMO患者和小鼠中鉴定了IFN-β治疗通过产生炎性细胞因子IL-6在T辅助细胞（TH）17诱导的疾病中具有炎性作用。然而，其他研究表明IFN-β抑制TH 17细胞的分化和功能。在这份手稿中，我们确定了IFN-β对TH 17发育的离散阶段具有不同的影响。在早期TH 17发育过程中，IFN-β抑制IL-17的产生。相反，在晚期TH 17分化期间，IFN-β与IL-23协同作用以促进具有TH 1和TH 17特征并表达升高水平的强效炎性细胞因子IL-6和GM-CSF以及转录因子BLIMP的致病性T细胞。总之，这些发现有助于解决围绕IFN-β和TH 17诱导的疾病的矛盾，并阐明了负责NMO和MS患者的病理生理学的途径，这些患者是IFN-β无应答者。
Interferon (IFN)-β is a popular therapy for multiple sclerosis (MS). However, 25–40% of patients are nonresponsive to this therapy, and it worsens neuromyelitis optica (NMO), another neuroinflammatory disease. We previously identified, in both NMO patients and in mice, that IFN-β treatment had inflammatory effects in T Helper (TH) 17-induced disease through the production of the inflammatory cytokine IL-6. However, other studies have shown that IFN-β inhibits the differentiation and function of TH17 cells. In this manuscript, we identified that IFN-β had differential effects on discrete stages of TH17 development. During early TH17 development, IFN-β inhibits IL-17 production. Conversely, during late TH17 differentiation, IFN-β synergizes with IL-23 to promote a pathogenic T cell that has both TH1 and TH17 characteristics and expresses elevated levels of the potent inflammatory cytokines IL-6 and GM-CSF and the transcription factor BLIMP. Together, these findings help resolve a paradox surrounding IFN-β and TH17-induced disease and illuminate the pathways responsible for the pathophysiology of NMO and MS patients who are IFN-β nonresponders.
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