Marcou Quentin, Carmi-Levy Irit, Trichot Coline, Soumelis Vassili, Mora Thierry, Walczak Aleksandra M
Laboratoire de physique théorique, CNRS, UPMC and École normale supérieure, 75005 Paris, France. Equal contribution.
Phys Biol. 2018 May 16;15(5):056001. doi: 10.1088/1478-3975/aaaa0a.
Cells of the immune system are confronted with opposing pro- and anti-inflammatory signals. Dendritic cells (DC) integrate these cues to make informed decisions whether to initiate an immune response. Confronted with exogenous microbial stimuli, DC endogenously produce both anti- (IL-10) and pro-inflammatory (TNFα) cues whose joint integration controls the cell's final decision. Backed by experimental measurements we present a theoretical model to quantitatively describe the integration mode of these opposing signals. We propose a two step integration model that modulates the effect of the two types of signals: an initial bottleneck integrates both signals (IL-10 and TNFα), the output of which is later modulated by the anti-inflammatory signal. We show that the anti-inflammatory IL-10 signaling is long ranged, as opposed to the short-ranged pro-inflammatory TNFα signaling. The model suggests that the population averaging and modulation of the pro-inflammatory response by the anti-inflammatory signal is a safety guard against excessive immune responses.
免疫系统的细胞面临着相反的促炎和抗炎信号。树突状细胞（DC）整合这些信号，以便就是否启动免疫反应做出明智的决定。面对外源性微生物刺激时，DC内源性地产生抗炎（IL-10）和促炎（TNFα）信号，这些信号的联合整合控制着细胞的最终决定。在实验测量的支持下，我们提出了一个理论模型来定量描述这些相反信号的整合模式。我们提出了一个两步整合模型，该模型调节这两种信号的作用：一个初始瓶颈整合两种信号（IL-10和TNFα），其输出随后由抗炎信号调节。我们表明，抗炎性IL-10信号是长程的，而促炎性TNFα信号是短程的。该模型表明，抗炎信号对促炎反应的群体平均和调节是防止过度免疫反应的一种安全保障。
