当前位置:科学网首页 > 小柯机器人 >详情
科学家提出内分泌自身免疫疾病产生的新假说
作者:小柯机器人 发布时间:2020/5/20 23:50:27

近日,以色列魏茨曼科学研究所的Uri Alon小组提出,内分泌自身免疫疾病是免疫系统抵抗超分泌突变细胞的一个弱点。2020年5月19日,《免疫》发表了这一成果。

一些内分泌器官经常是自身免疫攻击的靶标。研究人员从反馈控制的角度解决了自身免疫性疾病的起源。内分泌组织通过根据激素驱动的调节信号平衡细胞增殖和清除的反馈回路来维持质量。
 
研究人员假设存在一种专门的机制,其可检测和去除错觉信号的突变细胞,从而过度增殖和过度分泌,这具有破坏机体稳态的潜力。在这种机制中,以自身免疫疾病的脆弱性为代价,优先通过自身反应性T细胞消除超分泌细胞。
 
“超分泌突变体的自身免疫监视”(ASHM)假说预测了健康个体中自身反应性T细胞的存在,以及自身激素作为激素分泌途径的多肽性质。它解释了为什么有些组织会患上普遍的自身免疫病,而另一些组织却没有,而是表现出普遍的突变体扩张疾病(例如甲状旁腺功能亢进)。
 
附:英文原文

Title: Endocrine Autoimmune Disease as a Fragility of Immune Surveillance against Hypersecreting Mutants

Author: Yael Korem Kohanim, Avichai Tendler, Avi Mayo, Nir Friedman, Uri Alon

Issue&Volume: 2020/05/19

Abstract: Some endocrine organs are frequent targets of autoimmune attack. Here, we addressed the origin of autoimmune disease from the viewpoint of feedback control. Endocrine tissues maintain mass through feedback loops that balance cell proliferation and removal according to hormone-driven regulatory signals. We hypothesized the existence of a dedicated mechanism that detects and removes mutant cells that missense the signal and therefore hyperproliferate and hypersecrete with potential to disrupt organismal homeostasis. In this mechanism, hypersecreting cells are preferentially eliminated by autoreactive T cells at the cost of a fragility to autoimmune disease. The “autoimmune surveillance of hypersecreting mutants” (ASHM) hypothesis predicts the presence of autoreactive T cells in healthy individuals and the nature of self-antigens as peptides from hormone secretion pathway. It explains why some tissues get prevalent autoimmune disease, whereas others do not and instead show prevalent mutant-expansion disease (e.g., hyperparathyroidism). The ASHM hypothesis is testable, and we discuss experimental follow-up.

DOI: 10.1016/j.immuni.2020.04.022

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30180-1

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx