Immune signalling pathways convert pathogenic stimuli into cytosolic events that lead to the resolution of infection. Upon ligand engagement, immune receptors together with their downstream adaptors and effectors undergo substantial conformational changes and spatial reorganization. During this process, nanometre-to-micrometre-sized signalling clusters have been commonly observed that are believed to be hotspots for signal transduction. Because of their large size and heterogeneous composition, it remains a challenge to fully understand the mechanisms by which these signalling clusters form and their functional consequences. Recently, phase separation has emerged as a new biophysical principle for organizing biomolecules into large clusters with fluidic properties. Although the field is still in its infancy, studies of phase separation in immunology are expected to provide new perspectives for understanding immune responses. Here, we present an up-to-date view of how liquid–liquid phase separation drives the formation of signalling condensates and regulates immune signalling pathways, including those downstream of T cell receptor, B cell receptor and the innate immune receptors cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) and retinoic acid-inducible gene I protein (RIG-I). We conclude with a summary of the current challenges the field is facing and outstanding questions for future studies.

免疫信号通路将致病性刺激转化为导致感染消退的胞质事件。配体结合后，免疫受体及其下游衔接子和效应子会发生显着的构象变化和空间重组。在此过程中，通常观察到纳米到微米大小的信号簇，它们被认为是信号转导的热点。由于它们的大尺寸和异质成分，完全理解这些信号簇形成的机制及其功能后果仍然是一个挑战。最近，相分离已成为一种新的生物物理学原理，用于将生物分子组织成具有流体特性的大分子团。尽管该领域仍处于起步阶段，免疫学中相分离的研究有望为理解免疫反应提供新的视角。在这里，我们提出了液-液相分离如何驱动信号凝聚物的形成和调节免疫信号通路的最新观点，包括 T 细胞受体、B 细胞受体和先天免疫受体环状 GMP-AMP 的下游通路合成酶 (cGAS) – 干扰素基因 (STING) 和视黄酸诱导基因 I 蛋白 (RIG-I) 的刺激因子。最后，我们总结了该领域当前面临的挑战以及未来研究的突出问题。包括那些下游的 T 细胞受体、B 细胞受体和先天免疫受体环 GMP-AMP 合酶 (cGAS)-干扰素基因刺激物 (STING) 和视黄酸诱导基因 I 蛋白 (RIG-I)。最后，我们总结了该领域当前面临的挑战以及未来研究的突出问题。包括那些下游的 T 细胞受体、B 细胞受体和先天免疫受体环 GMP-AMP 合酶 (cGAS)-干扰素基因刺激物 (STING) 和视黄酸诱导基因 I 蛋白 (RIG-I)。最后，我们总结了该领域当前面临的挑战以及未来研究的突出问题。