Impact of noncanonical NF-κB signaling during hapten-induced skin inflammation (C03)

半抗原引起的皮肤炎症期间非典型 NF-κB 信号传导的影响 (C03)

• 批准号: 273674711
• 金额: --
• 依托单位: Universitäts-Hautklinik
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/273674711?language=en
• 关键词: Impact; noncanonical; NF; signaling; during

Our studies revealed that noncanonical NF-κB signaling is essential for adaptive immunity as mice deficient in NF-κB2 signaling were unable to develop progressive chronic contact hypersensitivity reactions. Thus, we aim to uncover how noncanonical NF-kB signaling modulates acute and chronic T cell driven inflammatory processes by (i) identifying the essential cellular players employing cell-type specific conditional NF-κB2-/- and NIKaly/aly mice in vivo, (ii) investigating cell specific impairments in activation, differentiation and survival in vitro, (iii) analyzing differences in T cell activation and leukocyte homing patterns in vivo and (iv) uncovering the efficacy of specific NF-κB2 inhibition in vitro and in vivo.

我们的研究表明，非经典的NF-κB信号传导对于获得性免疫是必不可少的，因为NF-κB2信号传导缺陷的小鼠不能发生进行性慢性接触性超敏反应。因此，我们的目标是揭示非经典NF-kB信号传导如何通过以下方式调节急性和慢性T细胞驱动的炎症过程：（i）在体内使用细胞类型特异性条件性NF-κB2-/-和NIKaly/aly小鼠鉴定基本细胞参与者，（ii）在体外研究细胞特异性活化、分化和存活损伤，（iii）分析体内T细胞活化和白细胞归巢模式的差异，以及（iv）揭示体外和体内特异性NF-κB2抑制的功效。