研究人员发现，免疫细胞中的一种自然分子刹车能够预防小鼠发生自体免疫性糖尿病，表明免疫系统能够用自己的方法预防过度激发和自体免疫，新成果发表在11月在线出版的《自然—医学》期刊上。
树突状细胞是一种免疫细胞，被激发后能刺激一种适应性免疫反应。迄今为止，许多研究主要集中在鉴别促成树突状细胞变异、激活和生存的因子。
Pamela Ohashi和同事发现，调控炎症反应的核因子- KB1在未成熟的树突状细胞中正常表达并让细胞处于静止状态。缺失核因子- KB1的树突状细胞处于激发状态，释放出促炎性细胞因子并刺激T细胞的免疫反应；之后，这些被激活的T细胞攻击胰岛，引发小鼠发生自体免疫性糖尿病。
Nuclear factor-κB1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells
Mature dendritic cells (DCs) are crucial for the induction of adaptive immune responses and perturbed DC homeostasis can result in autoimmune disease. Either uncontrolled expansion1 or enhanced survival2, 3 of DCs can result in a variety of autoimmune diseases in mouse models. In addition, increased maturation signals, through overexpression of surface Toll-like receptors (TLRs)4 or stimulation by type I interferon (IFN)5, has been associated with systemic autoimmunity. Whereas recent studies have focused on identifying factors required for initiating the maturation process, the possibility that resting DCs also express molecules that 'hold' them in an immature state has generally not been considered. Here we show that nuclear factor–κB1 (NF-κB1) is crucial for maintaining the resting state of DCs. Self-antigen–pulsed unstimulated DCs that do not express NF-κB1 were able to activate CD8+ T lymphocytes and induce autoimmunity. We further show that NF-κB1 negatively regulates the spontaneous production of tumor necrosis factor-α (TNF-α), which is associated with increased granzyme B expression in cytotoxic T lymphocytes (CTLs). These findings provide a new perspective on functional DC maturation and a potential mechanism that may account for pathologic T cell activation.
文献链接：https://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2556.html
