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.
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Zbinden, A., Perez-Berlanga, M., De Rossi, P. & Polymenidou, M. Phase separation and neurodegenerative diseases: a disturbance in the force. Dev. Cell 55, 45–68 (2020).
Su, X. et al. Phase separation of signaling molecules promotes T cell receptor signal transduction. Science 352, 595–599 (2016).
Huang, W. Y. C. et al. A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS. Science 363, 1098–1103 (2019).
Wong, L. E. et al. Tripartite phase separation of two signal effectors with vesicles priming B cell responsiveness. Nat. Commun. 11, 848 (2020).
Stone, M. B., Shelby, S. A., Nunez, M. F., Wisser, K. & Veatch, S. L. Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes. eLife 6, e19891 (2017).
Du, M. & Chen, Z. J. DNA-induced liquid phase condensation of cGAS activates innate immune signaling. Science 361, 704–709 (2018).
Yu, X. et al. The STING phase-separator suppresses innate immune signalling. Nat. Cell Biol. 23, 330–340 (2021).
Haubrich, K. et al. RNA binding regulates TRIM25-mediated RIG-I ubiquitylation. Preprint at bioRxiv https://doi.org/10.1101/2020.05.04.070177 (2020).
Jobe, F., Simpson, J., Hawes, P., Guzman, E. & Bailey, D. Respiratory syncytial virus sequesters NF-kappaB subunit p65 to cytoplasmic inclusion bodies to inhibit innate immune signaling. J. Virol. 94, e01380 (2020).
Rouches, M., Veatch, S. & Machta, B. Surface densities prewet a near-critical membrane. Preprint at bioRxiv https://doi.org/10.1101/2021.02.17.431700 (2021).
Brangwynne, C. P. et al. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324, 1729–1732 (2009).
Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017).
Pappu, R. V. Phase separation — a physical mechanism for organizing information and biochemical reactions. Dev. Cell 55, 1–3 (2020).
Li, W. et al. Biophysical properties of AKAP95 protein condensates regulate splicing and tumorigenesis. Nat. Cell Biol. 22, 960–972 (2020).
Sun, D., Wu, R., Zheng, J., Li, P. & Yu, L. Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation. Cell Res. 28, 405–415 (2018).
Ma, W. & Mayr, C. A membraneless organelle associated with the endoplasmic reticulum enables 3’UTR-mediated protein-protein interactions. Cell 175, 1492–1506 e19 (2018).
Zhao, Y. G. & Zhang, H. Phase separation in membrane biology: the interplay between membrane-bound organelles and membraneless condensates. Dev. Cell 55, 30–44 (2020).
Li, P. et al. Phase transitions in the assembly of multivalent signalling proteins. Nature 483, 336–340 (2012).
Banjade, S. & Rosen, M. K. Phase transitions of multivalent proteins can promote clustering of membrane receptors. eLife 3, e04123 (2014).
Beutel, O., Maraspini, R., Pombo-Garcia, K., Martin-Lemaitre, C. & Honigmann, A. Phase separation of zonula occludens proteins drives formation of tight junctions. Cell 179, 923–936 e11 (2019).
Schwayer, C. et al. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Cell 179, 937–952 e18 (2019).
Shan, Z. et al. Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division. Nat. Commun. 9, 737 (2018).
Zeng, M. et al. Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity. Cell 166, 1163–1175 e12 (2016).
Wu, X. et al. RIM and RIM-BP form presynaptic active-zone-like condensates via phase separation. Mol. Cell 73, 971–984 e5 (2019).
Bunnell, S. C. et al. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J. Cell Biol. 158, 1263–1275 (2002).
Depoil, D. et al. CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand. Nat. Immunol. 9, 63–72 (2008).
Xu, Q., Lin, W. C., Petit, R. S. & Groves, J. T. EphA2 receptor activation by monomeric ephrin-A1 on supported membranes. Biophys. J. 101, 2731–2739 (2011).
Algeciras-Schimnich, A. et al. Molecular ordering of the initial signaling events of CD95. Mol. Cell. Biol. 22, 207–220 (2002).
Harder, T. & Simons, K. Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains. Curr. Opin. Cell Biol. 9, 534–542 (1997).
Munro, S. Lipid rafts: elusive or illusive? Cell 115, 377–388 (2003).
Levental, I., Levental, K. R. & Heberle, F. A. Lipid rafts: controversies resolved, mysteries remain. Trends Cell Biol. 30, 341–353 (2020).
Kim, S., Kalappurakkal, J. M., Mayor, S. & Rosen, M. K. Phosphorylation of nephrin induces phase separated domains that move through actomyosin contraction. Mol. Biol. Cell 30, 2996–3012 (2019).
Yang, W. et al. Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism. Nature 531, 651–655 (2016).
Chung, J. K. et al. Coupled membrane lipid miscibility and phosphotyrosine-driven protein condensation phase transitions. Biophys. J. 120, 1257–1265 (2020).
Gureasko, J. et al. Membrane-dependent signal integration by the Ras activator Son of sevenless. Nat. Struct. Mol. Biol. 15, 452–461 (2008).
Zeng, M. et al. Reconstituted postsynaptic density as a molecular platform for understanding synapse formation and plasticity. Cell 174, 1172–1187 e16 (2018).
Orbach, R. & Su, X. Surfing on membrane waves: microvilli, curved membranes, and immune signaling. Front. Immunol. 11, 2187 (2020).
Jain, A. & Vale, R. D. RNA phase transitions in repeat expansion disorders. Nature 546, 243–247 (2017).
Zhang, H. et al. RNA controls polyQ protein phase transitions. Mol. Cell 60, 220–230 (2015).
Langdon, E. M. et al. mRNA structure determines specificity of a polyQ-driven phase separation. Science 360, 922–927 (2018).
Kato, M. et al. Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 149, 753–767 (2012).
Han, T. W. et al. Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. Cell 149, 768–779 (2012).
Sanders, D. W. et al. Competing protein-RNA interaction networks control multiphase intracellular organization. Cell 181, 306–324 e28 (2020).
Riback, J. A. et al. Stress-triggered phase separation is an adaptive, evolutionarily tuned response. Cell 168, 1028–1040 e19 (2017).
Ruff, K. M., Roberts, S., Chilkoti, A. & Pappu, R. V. Advances in understanding stimulus-responsive phase behavior of intrinsically disordered protein polymers. J. Mol. Biol. 430, 4619–4635 (2018).
Kato, M. et al. Redox state controls phase separation of the yeast ataxin-2 protein via reversible oxidation of its methionine-rich low-complexity domain. Cell 177, 711–721 e8 (2019).
Rai, A. K., Chen, J. X., Selbach, M. & Pelkmans, L. Kinase-controlled phase transition of membraneless organelles in mitosis. Nature 559, 211–216 (2018).
Ferreon, J. C. et al. Acetylation disfavors tau phase separation. Int. J. Mol. Sci. 19, 1360 (2018).
Qamar, S. et al. FUS phase separation is modulated by a molecular chaperone and methylation of arginine cation-pi interactions. Cell 173, 720–734 e15 (2018).
Liu, B., Chen, W., Evavold, B. D. & Zhu, C. Accumulation of dynamic catch bonds between TCR and agonist peptide-MHC triggers T cell signaling. Cell 157, 357–368 (2014).
Nishi, H. et al. Neutrophil FcgammaRIIA promotes IgG-mediated glomerular neutrophil capture via Abl/Src kinases. J. Clin. Invest. 127, 3810–3826 (2017).
Wan, Z. et al. The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold. Elife 4, e06925 (2015).
Case, L. B., Ditlev, J. A. & Rosen, M. K. Regulation of transmembrane signaling by phase separation. Annu. Rev. Biophys. 48, 465–494 (2019).
Dustin, M. L. & Groves, J. T. Receptor signaling clusters in the immune synapse. Annu. Rev. Biophys. 41, 543–556 (2012).
Jaqaman, K. & Ditlev, J. A. Biomolecular condensates in membrane receptor signaling. Curr. Opin. Cell Biol. 69, 48–54 (2021).
Hui, E. et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science 355, 1428–1433 (2017).
Grakoui, A. et al. The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221–227 (1999).
Barda-Saad, M. et al. Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton. Nat. Immunol. 6, 80–89 (2005).
Douglass, A. D. & Vale, R. D. Single-molecule microscopy reveals plasma membrane microdomains created by protein-protein networks that exclude or trap signaling molecules in T cells. Cell 121, 937–950 (2005).
Houtman, J. C. et al. Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1. Nat. Struct. Mol. Biol. 13, 798–805 (2006).
Su, X., Ditlev, J. A., Rosen, M. K. & Vale, R. D. Reconstitution of TCR signaling using supported lipid bilayers. Methods Mol. Biol. 1584, 65–76 (2017).
Kortum, R. L. et al. The ability of Sos1 to oligomerize the adaptor protein LAT is separable from its guanine nucleotide exchange activity in vivo. Sci. Signal. 6, ra99 (2013).
Zeng, L., Palaia, I., Saric, A. & Su, X. PLCgamma1 promotes phase separation of T cell signaling components. J. Cell Biol. 220, e202009154 (2021).
Ditlev, J. A. et al. A composition-dependent molecular clutch between T cell signaling condensates and actin. eLife 8, e42695 (2019).
Wei, M. T. et al. Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles. Nat. Chem. 9, 1118–1125 (2017).
Case, L. B., Zhang, X., Ditlev, J. A. & Rosen, M. K. Stoichiometry controls activity of phase-separated clusters of actin signaling proteins. Science 363, 1093–1097 (2019).
Balagopalan, L. et al. c-Cbl-mediated regulation of LAT-nucleated signaling complexes. Mol. Cell Biol. 27, 8622–8636 (2007).
Paster, W. et al. A THEMIS:SHP1 complex promotes T-cell survival. EMBO J. 34, 393–409 (2015).
Dong, R. et al. Rewired signaling network in T cells expressing the chimeric antigen receptor (CAR). EMBO J. 39, e104730 (2020).
Davis, S. J. & van der Merwe, P. A. The kinetic-segregation model: TCR triggering and beyond. Nat. Immunol. 7, 803–809 (2006).
Pielak, R. M. et al. Early T cell receptor signals globally modulate ligand:receptor affinities during antigen discrimination. Proc. Natl Acad. Sci. USA 114, 12190–12195 (2017).
Lin, J. J. Y. et al. Mapping the stochastic sequence of individual ligand-receptor binding events to cellular activation: T cells act on the rare events. Sci. Signal. 12, eaat8715 (2019).
Engelke, M. et al. Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in resting B cells. Sci. Signal. 7, ra79 (2014).
Oellerich, T. et al. The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85. EMBO J. 30, 3620–3634 (2011).
Gold, M. R. & Reth, M. G. Antigen receptor function in the context of the nanoscale organization of the B cell membrane. Annu. Rev. Immunol. 37, 97–123 (2019).
Pierce, S. K. & Liu, W. The tipping points in the initiation of B cell signalling: how small changes make big differences. Nat. Rev. Immunol. 10, 767–777 (2010).
Shelby, S. A., Castello-Serrano, I., Wisser, K., Levental, I. & Veatch, S. Membrane phase separation drives organization at B cell receptor clusters. Preprint at bioRxiv https://doi.org/10.1101/2021.05.12.443834 (2021).
Williamson, A. P. & Vale, R. D. Spatial control of Draper receptor signaling initiates apoptotic cell engulfment. J. Cell Biol. 217, 3977–3992 (2018).
Goodridge, H. S. et al. Activation of the innate immune receptor dectin-1 upon formation of a ‘phagocytic synapse’. Nature 472, 471–475 (2011).
Shelby, S. A., Holowka, D., Baird, B. & Veatch, S. L. Distinct stages of stimulated FcepsilonRI receptor clustering and immobilization are identified through superresolution imaging. Biophys. J. 105, 2343–2354 (2013).
Veatch, S. L., Chiang, E. N., Sengupta, P., Holowka, D. A. & Baird, B. A. Quantitative nanoscale analysis of IgE-FcepsilonRI clustering and coupling to early signaling proteins. J. Phys. Chem. B 116, 6923–6935 (2012).
Menon, A. K., Holowka, D. & Baird, B. Small oligomers of immunoglobulin E (IgE) cause large-scale clustering of IgE receptors on the surface of rat basophilic leukemia cells. J. Cell Biol. 98, 577–583 (1984).
Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z. J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786–791 (2013).
Wu, J. et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339, 826–830 (2013).
Xie, W. et al. Human cGAS catalytic domain has an additional DNA-binding interface that enhances enzymatic activity and liquid-phase condensation. Proc. Natl Acad. Sci. USA 116, 11946–11955 (2019).
Zhou, W., Mohr, L., Maciejowski, J. & Kranzusch, P. J. cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances cytosolic DNA sensing. Mol. Cell 81, 739–755 e7 (2021).
Chen, S., Rong, M., Lv, Y., Zhu, D. & Xiang, Y. Regulation of cGAS activity through RNA-mediated phase separation. Preprint at bioRxiv https://doi.org/10.1101/2021.05.12.443834 (2020).
Zhang, Y. et al. Streptavidin promotes DNA binding and activation of cGAS to enhance innate immunity. iScience 23, 101463 (2020).
Xu, G. et al. Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion. Mol. Cell https://doi.org/10.1016/j.molcel.2021.05.002 (2021).
Yang, P. et al. G3BP1 is a tunable switch that triggers phase separation to assemble stress granules. Cell 181, 325–345 e28 (2020).
Liu, Z. S. et al. G3BP1 promotes DNA binding and activation of cGAS. Nat. Immunol. 20, 18–28 (2019).
Ergun, S. L., Fernandez, D., Weiss, T. M. & Li, L. STING polymer structure reveals mechanisms for activation, hyperactivation, and inhibition. Cell 178, 290–301 e10 (2019).
Li, S. et al. Prolonged activation of innate immune pathways by a polyvalent STING agonist. Nat. Biomed. Eng. 5, 455–466 (2021).
Yang, W. et al. G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response. Cell Death Dis. 10, 946 (2019).
Gack, M. U. et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446, 916–920 (2007).
Arimoto, K. et al. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc. Natl Acad. Sci. USA 104, 7500–7505 (2007).
Kim, S. S., Sze, L., Liu, C. & Lam, K. P. The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-beta response. J. Biol. Chem. 294, 6430–6438 (2019).
Onomoto, K. et al. Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity. PLoS ONE 7, e43031 (2012).
Reineke, L. C. & Lloyd, R. E. The stress granule protein G3BP1 recruits protein kinase R to promote multiple innate immune antiviral responses. J. Virol. 89, 2575–2589 (2015).
Rozelle, D. K., Filone, C. M., Kedersha, N. & Connor, J. H. Activation of stress response pathways promotes formation of antiviral granules and restricts virus replication. Mol. Cell Biol. 34, 2003–2016 (2014).
Monette, A. et al. Pan-retroviral nucleocapsid-mediated phase separation regulates genomic RNA positioning and trafficking. Cell Rep. 31, 107520 (2020).
Heinrich, B. S., Maliga, Z., Stein, D. A., Hyman, A. A. & Whelan, S. P. J. Phase transitions drive the formation of vesicular stomatitis virus replication compartments. mBio https://doi.org/10.1128/mBio.02290-17 (2018).
Nikolic, J. et al. Negri bodies are viral factories with properties of liquid organelles. Nat. Commun. 8, 58 (2017).
Lifland, A. W. et al. Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize the innate immune response mediated by MDA5 and MAVS. J. Virol. 86, 8245–8258 (2012).
Fricke, J., Koo, L. Y., Brown, C. R. & Collins, P. L. p38 and OGT sequestration into viral inclusion bodies in cells infected with human respiratory syncytial virus suppresses MK2 activities and stress granule assembly. J. Virol. 87, 1333–1347 (2013).
Brangwynne, C. P., Mitchison, T. J. & Hyman, A. A. Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes. Proc. Natl Acad. Sci. USA 108, 4334–4339 (2011).
Ambadipudi, S., Biernat, J., Riedel, D., Mandelkow, E. & Zweckstetter, M. Liquid-liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein tau. Nat. Commun. 8, 275 (2017).
Maharana, S. et al. RNA buffers the phase separation behavior of prion-like RNA binding proteins. Science 360, 918–921 (2018).
Mitrea, D. M. et al. Self-interaction of NPM1 modulates multiple mechanisms of liquid-liquid phase separation. Nat. Commun. 9, 842 (2018).
Khan, T. et al. Quantifying nucleation in vivo reveals the physical basis of prion-like phase behavior. Mol. Cell 71, 155–168 e7 (2018).
Posey, A. E. et al. Mechanistic inferences from analysis of measurements of protein phase transitions in live cells. J. Mol. Biol. 433, 166848 (2021).
Yan, Z. et al. Dynamic monitoring of phase-separated biomolecular condensates by photoluminescence lifetime imaging. Anal. Chem. 93, 2988–2995 (2021).
Taylor, N. et al. Biophysical characterization of organelle-based RNA/protein liquid phases using microfluidics. Soft Matter 12, 9142–9150 (2016).
Delarue, M. et al. mTORC1 controls phase separation and the biophysical properties of the cytoplasm by tuning crowding. Cell 174, 338–349 e20 (2018).
Smirnov, E. et al. Reproduction of the FC/DFC units in nucleoli. Nucleus 7, 203–215 (2016).
Oberti, D. et al. Dicer and Hsp104 function in a negative feedback loop to confer robustness to environmental stress. Cell Rep. 10, 47–61 (2015).
Franzmann, T. M. et al. Phase separation of a yeast prion protein promotes cellular fitness. Science 359, eaao5654 (2018).
Patel, A. et al. A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell 162, 1066–1077 (2015).
Wang, J. et al. A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell 174, 688–699 e16 (2018).
Louvet, E., Yoshida, A., Kumeta, M. & Takeyasu, K. Probing the stiffness of isolated nucleoli by atomic force microscopy. Histochem. Cell Biol. 141, 365–381 (2014).
Conicella, A. E., Zerze, G. H., Mittal, J. & Fawzi, N. L. ALS mutations disrupt phase separation mediated by alpha-helical structure in the TDP-43 low-complexity C-terminal domain. Structure 24, 1537–1549 (2016).
Brady, J. P. et al. Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation. Proc. Natl Acad. Sci. USA 114, E8194–E8203 (2017).
Boeynaems, S. et al. Protein phase separation: a new phase in cell biology. Trends Cell Biol. 28, 420–435 (2018).
Alberti, S., Gladfelter, A. & Mittag, T. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell 176, 419–434 (2019).
McSwiggen, D. T., Mir, M., Darzacq, X. & Tjian, R. Evaluating phase separation in live cells: diagnosis, caveats, and functional consequences. Genes Dev. 33, 1619–1634 (2019).
Mitrea, D. M. et al. Methods for physical characterization of phase-separated bodies and membrane-less organelles. J. Mol. Biol. 430, 4773–4805 (2018).
Nakamura, H. et al. Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions. Nat. Mater. 17, 79–89 (2018).
Shin, Y. et al. Spatiotemporal control of intracellular phase transitions using light-activated optodroplets. Cell 168, 159–171 e14 (2017).
Bracha, D. et al. Mapping local and global liquid phase behavior in living cells using photo-oligomerizable seeds. Cell 175, 1467–1480 e13 (2018).
Dine, E., Gil, A. A., Uribe, G., Brangwynne, C. P. & Toettcher, J. E. Protein phase separation provides long-term memory of transient spatial stimuli. Cell Syst. 6, 655–663 e5 (2018).
Schneider, N. et al. Liquid-liquid phase separation of light-inducible transcription factors increases transcription activation in mammalian cells and mice. Sci. Adv. 7, eabd3568 (2021).
Yu, N. et al. Near-infrared-light activatable nanoparticles for deep-tissue-penetrating wireless optogenetics. Adv. Healthc. Mater. 8, e1801132 (2019).
X.S. has received support from an American Cancer Society Institutional Research Grant, the Charles H. Hood Foundation Child Health Research Awards Program, an Andrew McDonough B+ Foundation research grant, the Gilead Sciences Research Scholars Program in Hematology/Oncology, the Rally Foundation and Bear Necessities Foundation Collaborative Pediatric Cancer Research Awards Program, a Yale SPORE in Skin Cancer Development Research Program Award, a Yale DeLuca Pilot Award and the NIGMS MIRA (R35) programme (GM138299).
The authors declare no competing interests.
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Xiao, Q., McAtee, C.K. & Su, X. Phase separation in immune signalling. Nat Rev Immunol (2021). https://doi.org/10.1038/s41577-021-00572-5