论文标题
Tregs自组织成“计算生态系统”，并实施一种复杂的优化算法来介导免疫反应
Tregs self-organize into a "computing ecosystem" and implement a sophisticated optimization algorithm for mediating immune response
论文作者
论文摘要
调节性T细胞（Tregs）在介导免疫反应中起着至关重要的作用。然而，仍然缺乏对Treg在适应性免疫中的作用的算法理解。在这里，我们提出了Treg介导的自我耐受性的生物物理现实模型，其中Treg与自我抗原结合并局部抑制附近活化T细胞的增殖。通过利用生态动力学和约束优化之间的二元性，我们表明Tregs瓷砖潜在的抗原空间，同时最大程度地减少Treg激活曲线之间的重叠。我们发现，对于非常高的Treg多样性，Treg介导的自我耐受性对于自我抗原浓度的波动是可靠的，但降低了Treg的多样性会导致急剧过渡 - 与PercePtrons的Gardner Transition相关 - 与自我抗原浓度的变化可能导致自动免疫响应。我们提出了对免疫缺陷小鼠中这种过渡的新实验测试，并讨论了对自身免疫性疾病的潜在影响。
Regulatory T cells (Tregs) play a crucial role in mediating immune response. Yet an algorithmic understanding of the role of Tregs in adaptive immunity remains lacking. Here, we present a biophysically realistic model of Treg mediated self-tolerance in which Tregs bind to self-antigens and locally inhibit the proliferation of nearby activated T cells. By exploiting a duality between ecological dynamics and constrained optimization, we show that Tregs tile the potential antigen space while simultaneously minimizing the overlap between Treg activation profiles. We find that for sufficiently high Treg diversity, Treg mediated self-tolerance is robust to fluctuations in self-antigen concentrations but lowering the Treg diversity results in a sharp transition -- related to the Gardner transition in perceptrons -- to a regime where changes in self-antigen concentrations can result in an auto-immune response. We propose a novel experimental test of this transition in immune-deficient mice and discuss potential implications for autoimmune diseases.
