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

我们的研究表明，非规范的NF-κB信号对获得性免疫是必不可少的，因为NF-κB2信号缺陷的小鼠不能产生进行性慢性接触性超敏反应。因此，我们的目标是通过(I)在体内识别使用细胞型特异性条件性NF-κB2-/-和NiKaly/Aly小鼠的基本细胞角色，(Ii)在体外研究细胞在激活、分化和存活中的特异性损伤，(Iii)分析体内T细胞激活和白细胞归巢模式的差异，以及(Iv)揭示特定的NF-κB2体外和体内抑制的有效性，揭示非规范的NF-kB信号如何调控急慢性T细胞驱动的炎症过程。

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.