美国和比利时科学家近日在小鼠免疫系统内发现了一个特殊的机制，关闭这一机制会导致自体免疫疾病产生。这一发现阐明了自体免疫性的产生过程，对于研发新的药物以加强对癌症、艾滋等病的免疫响应也有所启示。相关论文8月13日在线发表于《自然》（Nature）杂志上。
美国国立卫生研究院的科学家研究了免疫系统T细胞，特别是辅助T细胞，并重点关注了furin蛋白，这是一种在T细胞机能中发挥重要作用的酶。furin蛋白很难研究，因为其它一些酶也能执行与其相似的功能，而且，furin蛋白对生命是必不可少的，所以科学家无法创建一个小鼠模型，使其不带furin蛋白而能活过胚胎阶段。
在最新的实验中，研究人员别出心裁，创建了一个仅T细胞不含furin的小鼠模型。结果发现，这些小鼠产生了系统性自体免疫疾病。
论文第一作者、美国国立关节炎、肌与骨骼及皮肤病研究所（NIAMS）的Marko Pesu说：“我们已经知道furin似乎在很多疾病中发挥着作用，如癌症、囊肿性纤维化以及传染病。此次发现说明，某些免疫细胞缺失furin会增加免疫响应并导致小鼠患上自体免疫疾病。”
研究人员还发现，删除辅助T细胞中的furin会影响另两种T细胞——调节性T细胞和效应性T细胞的功能。前者借助Furin促进机体组织与细胞的免疫耐受性，后者缺乏furin会增加攻击性，易导致自体免疫性疾病和组织损伤。
文章另一位作者、NIAMS的科学主任John J. O'Shea说：“抑制furin曾被认为会减少恶性细胞的生长，或通过阻碍病原体的活化来阻止感染。然而，此次研究结果显示，药物干预可能会产生意想不到的副作用——增加患自体免疫疾病的风险。”
生物探索推荐英文摘要
Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins1. It is induced in activated T cells and is reported to process a variety of substrates including the anti-inflammatory cytokine transforming growth factor (TGF)-beta1 (refs 2–4), but the non-redundant functions of furin versus other proprotein convertases in T cells are unclear. Here we show that conditional deletion of furin in T cells allowed for normal T-cell development but impaired the function of regulatory and effector T cells, which produced less TGF-beta1. Furin-deficient T regulatory (Treg) cells were less protective in a T-cell transfer colitis model and failed to induce Foxp3 in normal T cells. Additionally, furin-deficient effector cells were inherently over-active and were resistant to suppressive activity of wild-type Treg cells. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its non-redundant, essential function in regulating TGF-beta1 production. Targeting furin has emerged as a strategy in malignant and infectious disease5, 6. Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.
