PDF(Pubmed)
Abstract：
ILC2s are capable of generating memory. The mechanism of memory induction and memory-driven effector function (trained immunity) in ILC2s is unknown.
NFκB1 is preferentially expressed at a high level in ILC2s. We examined the role of NFkB1 in memory induction and memory-driven effector function in a mouse model of asthma.
Intranasal administration of Alternaria, flexivent, ELISA, histology, real-time PCR, western blot, flow cytometry and immunofluorescence staining.
NFκB1 was essential for the effector phase of memory-driven asthma. NFκB1 was critical for IL33 production, ILC2 generation, and production of type-2 cytokines, which resulted in eosinophilic inflammation and other features of asthma. NFκB1 induction of type-2 cytokines in ILC2s was independent of GATA3. NFκB1 was important for allergen induction of ILC3s and FoxP3+ Tregs. NFκB1 did not affect Th2 cells or their cytokine production. In contrast to its protagonistic role in the effector phase, NFκB1 had an antagonistic role in the memory phase. NFκB1 inhibited allergen-induced upregulation of memory-associated repressor and preparedness genes in ILC2s. NFκB1 upregulated RUNX1. NFκB1 formed a heterodimer with RUNX1 in ILC2s.
NFκB1 positively regulated the effector phase but inhibited the induction phase of memory. The foregoing pointed to an interdependent antagonism between the memory induction and the memory effector processes. The NFκB1-RUNX1 heterodimer represented a non-canonical transcriptional activator of type-2 cytokines in ILC2s.
NFκB1 is preferentially expressed at a high level in ILC2s. We examined the role of NFkB1 in memory induction and memory-driven effector function in a mouse model of asthma.
Intranasal administration of Alternaria, flexivent, ELISA, histology, real-time PCR, western blot, flow cytometry and immunofluorescence staining.
NFκB1 was essential for the effector phase of memory-driven asthma. NFκB1 was critical for IL33 production, ILC2 generation, and production of type-2 cytokines, which resulted in eosinophilic inflammation and other features of asthma. NFκB1 induction of type-2 cytokines in ILC2s was independent of GATA3. NFκB1 was important for allergen induction of ILC3s and FoxP3+ Tregs. NFκB1 did not affect Th2 cells or their cytokine production. In contrast to its protagonistic role in the effector phase, NFκB1 had an antagonistic role in the memory phase. NFκB1 inhibited allergen-induced upregulation of memory-associated repressor and preparedness genes in ILC2s. NFκB1 upregulated RUNX1. NFκB1 formed a heterodimer with RUNX1 in ILC2s.
NFκB1 positively regulated the effector phase but inhibited the induction phase of memory. The foregoing pointed to an interdependent antagonism between the memory induction and the memory effector processes. The NFκB1-RUNX1 heterodimer represented a non-canonical transcriptional activator of type-2 cytokines in ILC2s.
摘要：
■ILC2能够产生记忆。ILC2s中记忆诱导和记忆驱动效应子功能(训练免疫)的机制是未知的。
■NFκB1优先在ILC2s中高水平表达。我们在哮喘小鼠模型中研究了NFkB1在记忆诱导和记忆驱动效应功能中的作用。
■鼻内给药链格孢菌，flexvent,ELISA,组织学,实时PCR，westernblot,流式细胞术和免疫荧光染色。
■NFκB1对于记忆驱动的哮喘的效应期至关重要。NFκB1对IL33的生产至关重要，ILC2代，和产生2型细胞因子，导致嗜酸性粒细胞炎症和哮喘的其他特征。NFκB1在ILC2s中诱导2型细胞因子独立于GATA3。NFκB1对于ILC3s和FoxP3+Tregs的变应原诱导是重要的。NFκB1不影响Th2细胞或其细胞因子的产生。与其在效应物相中的质子作用相反，NFκB1在记忆阶段具有拮抗作用。NFκB1抑制过敏原诱导的ILC2s中记忆相关阻遏物和准备基因的上调。NFκB1上调RUNX1。NFκB1与ILC2s中的RUNX1形成异二聚体。
■NFκB1正调节效应相，但抑制记忆的诱导相。上述指出了记忆诱导和记忆效应过程之间的相互依赖的拮抗作用。NFκB1-RUNX1异二聚体代表ILC2s中2型细胞因子的非规范转录激活因子。
■NFκB1优先在ILC2s中高水平表达。我们在哮喘小鼠模型中研究了NFkB1在记忆诱导和记忆驱动效应功能中的作用。
■鼻内给药链格孢菌，flexvent,ELISA,组织学,实时PCR，westernblot,流式细胞术和免疫荧光染色。
■NFκB1对于记忆驱动的哮喘的效应期至关重要。NFκB1对IL33的生产至关重要，ILC2代，和产生2型细胞因子，导致嗜酸性粒细胞炎症和哮喘的其他特征。NFκB1在ILC2s中诱导2型细胞因子独立于GATA3。NFκB1对于ILC3s和FoxP3+Tregs的变应原诱导是重要的。NFκB1不影响Th2细胞或其细胞因子的产生。与其在效应物相中的质子作用相反，NFκB1在记忆阶段具有拮抗作用。NFκB1抑制过敏原诱导的ILC2s中记忆相关阻遏物和准备基因的上调。NFκB1上调RUNX1。NFκB1与ILC2s中的RUNX1形成异二聚体。
■NFκB1正调节效应相，但抑制记忆的诱导相。上述指出了记忆诱导和记忆效应过程之间的相互依赖的拮抗作用。NFκB1-RUNX1异二聚体代表ILC2s中2型细胞因子的非规范转录激活因子。
