Jagged-1 Reduces Th2 Inflammation and Memory Cell Expansion in Allergic Airway Disease.
Jagged-1 Reduces Th2 Inflammation and Memory Cell Expansion in Allergic Airway Disease.
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DOI：
10.4049/immunohorizons.2300001
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发表时间：
2023-02-01
期刊：
影响因子：
--
通讯作者：
Schaller M
中科院分区：
文献类型：
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作者：
Kimura S;Dupee Z;Lima F;Allen R;Kazmi S;Diodati N;Lukacs NW;Kunkel SL;Schaller M
Notch配体存在于T细胞和树突状细胞（dc）之间的相互作用过程中，通过诱导T细胞调节、存活和细胞因子反应等多种作用来决定细胞表型。Notch配体在dc上的存在随着炎症反应的背景而变化；Jagged-1是组成性表达的，而delta -1和delta - 4则是对病原体暴露的反应。尽管Delta-like和Jagged配体通过相同的Notch受体发送不同的信号，但这两种配体在外周T细胞免疫中的作用尚不清楚。我们的研究目的是确定Jagged-1在小鼠变应性气道疾病中OVA诱导的无病原体炎症中的作用。我们的研究表明，dc表达的jagded -1缺失导致细胞因子产生显著增加，导致OVA致敏和攻毒小鼠肺部粘液产生增加，嗜酸性粒细胞增多。我们还观察到Jagged-1表达的减少与肺和淋巴结CD4+ T细胞表面Notch 1受体表达的增加相关。通过使用OT-II转基因T细胞的转移研究，我们发现Jagged-1抑制CD44+CD62L+CCR7+记忆细胞的扩增，促进CD44+CD62L−效应细胞的扩增，但对过敏性气道疾病中幼稚细胞的扩增没有影响。这些数据表明Jagged-1可能在ag特异性T细胞反应中有不同的作用，这取决于受刺激T细胞的成熟度。
Notch ligands present during interactions between T cells and dendritic cells (DCs) dictate cell phenotype through a myriad of effects including the induction of T cell regulation, survival, and cytokine response. The presence of Notch ligands on DCs varies with the context of the inflammatory response; Jagged-1 is constitutively expressed, whereas Delta-like 1 and Delta-like 4 are induced in response to pathogen exposure. Although Delta-like and Jagged ligands send different signals through the same Notch receptor, the role of these two ligands in peripheral T cell immunity is not clear. The goal of our studies was to determine the role of Jagged-1 in the pathogen-free inflammation induced by OVA during allergic airway disease in mice. Our studies show that a deletion in DC-expressed Jagged-1 causes a significant increase in cytokine production, resulting in increased mucus production and increased eosinophilia in the lungs of mice sensitized and challenged with OVA. We also observed that a reduction of Jagged-1 expression is correlated with increased expression of the Notch 1 receptor on the surface of CD4+ T cells in both the lung and lymph node. Through transfer studies using OT-II transgenic T cells, we demonstrate that Jagged-1 represses the expansion of CD44+CD62L+CCR7+ memory cells and promotes the expansion of CD44+CD62L− effector cells, but it has no effect on the expansion of naive cells during allergic airway disease. These data suggest that Jagged-1 may have different roles in Ag-specific T cell responses, depending on the maturity of the stimulated T cell.