Lun, M. P., Monuki, E. S. & Lehtinen, M. K. Development and functions of the choroid plexus–cerebrospinal fluid system. Nat. Rev. Neurosci. 16, 445–457 (2015).
Dani, N. et al. A cellular and spatial map of the choroid plexus across brain ventricles and ages. Cell 184, 3056–3074.e21 (2021).
Saunders, N. R., Dziegielewska, K. M., Fame, R. M., Lehtinen, M. K. & Liddelow, S. A. The choroid plexus: a missing link in our understanding of brain development and function. Physiol. Rev. 103, 919–956 (2023).
Mastorakos, P. & McGavern, D. The anatomy and immunology of vasculature in the central nervous system. Sci. Immunol. 4, eaav0492 (2019).
De Vlaminck, K. et al. Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation. Immunity 55, 2085–2102.e9 (2022).
Baruch, K. et al. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science 346, 89–93 (2014).
Robert, S. M. et al. The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus. Cell 186, 764–785.e21 (2023).
Brioschi, S. et al. A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages. Immunity 56, 1027–1045.e8 (2023).
Utz, S. G. et al. Early fate defines microglia and non-parenchymal brain macrophage development. Cell 181, 557–573.e18 (2020).
Van Hove, H. et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nat. Neurosci. 22, 1021–1035 (2019).
Gomez Perdiguero, E. et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 518, 547–551 (2015).
Liu, Z. et al. Fate mapping via Ms4a3-expression history traces monocyte-derived cells. Cell 178, 1509–1525.e19 (2019).
Liu, Z. et al. Dendritic cell type 3 arises from Ly6C+ monocyte-dendritic cell progenitors. Immunity 56, 1761–1777.e6 (2023).
Cortez, V. S. et al. Transforming growth factor-β signaling guides the differentiation of innate lymphoid cells in salivary glands. Immunity 44, 1127–1139 (2016).
Matcovitch-Natan, O. et al. Microglia development follows a stepwise program to regulate brain homeostasis. Science 353, aad8670 (2016).
Kim, J. S. et al. A binary Cre transgenic approach dissects microglia and CNS border-associated macrophages. Immunity 54, 176–190.e7 (2021).
Su, W. et al. CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer’s disease pathology. Nat. Immunol. 24, 1735–1747 (2023).
Piehl, N. et al. Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment. Cell 185, 5028–5039.e13 (2022).
Ozga, A. J., Chow, M. T. & Luster, A. D. Chemokines and the immune response to cancer. Immunity 54, 859–874 (2021).
Dai, C. et al. CXCL14 displays antimicrobial activity against respiratory tract bacteria and contributes to clearance of Streptococcus pneumoniae pulmonary infection. J. Immunol. 194, 5980–5989 (2015).
Greenwood, S., Swetloff, A., Wade, A. M., Terasaki, T. & Ferretti, P. Fgf2 is expressed in human and murine embryonic choroid plexus and affects choroid plexus epithelial cell behaviour. Cerebrospinal Fluid Res. 5, 20 (2008).
Goldmann, T. et al. Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat. Immunol. 17, 797–805 (2016).
Masuda, T. et al. Specification of CNS macrophage subsets occurs postnatally in defined niches. Nature 604, 740–748 (2022).
Wang, Y. et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13, 753–760 (2012).
Greter, M. et al. Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37, 1050–1060 (2012).
Kana, V. et al. CSF-1 controls cerebellar microglia and is required for motor function and social interaction. J. Exp. Med. 216, 2265–2281 (2019).
Munro, D. A. D. et al. CNS macrophages differentially rely on an intronic Csf1r enhancer for their development. Development 147, dev.194449 (2020).
Rebejac, J. et al. Meningeal macrophages protect against viral neuroinfection. Immunity 55, 2103–2117.e10 (2022).
Kim, Y.-C. et al. Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates. Sci. Immunol. 8, eadg6155 (2023).
Herz, J., Johnson, K. R. & McGavern, D. B. Therapeutic antiviral T cells noncytopathically clear persistently infected microglia after conversion into antigen-presenting cells. J. Exp. Med. 212, 1153–1169 (2015).
Pinho-Ribeiro, F. A. et al. Bacteria hijack a meningeal neuroimmune axis to facilitate brain invasion. Nature 615, 472–481 (2023).
Rua, R. et al. Infection drives meningeal engraftment by inflammatory monocytes that impairs CNS immunity. Nat. Immunol. 20, 407–419 (2019).
Lauterbach, H., Truong, P. & McGavern, D. B. Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification. Virol. J. 4, 53 (2007).
Ozga, A. J. et al. CXCL10 chemokine regulates heterogeneity of the CD8+ T cell response and viral set point during chronic infection. Immunity 55, 82–97.e8 (2022).
Denton, A. E. et al. Type I interferon induces CXCL13 to support ectopic germinal center formation. J. Exp. Med. 216, 621–637 (2019).
Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017).
Wang, S. et al. TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways. Cell 185, 4153–4169.e19 (2022).
Fullard, J. F. et al. Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19. Genome Med. 13, 118 (2021).
Yang, A. C. et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19. Nature 595, 565–571 (2021).
Gosselin, D. et al. An environment-dependent transcriptional network specifies human microglia identity. Science 356, 1248–1259 (2017).
Masuda, T. et al. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution. Nature 566, 388–392 (2019).
Amann, L. et al. Extrasinusoidal macrophages are a distinct subset of immunologically active dural macrophages. Sci. Immunol. 9, eadh1129 (2024).
Li, Q. et al. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron 101, 207–223.e10 (2019).
Bastos, J. et al. Monocytes can efficiently replace all brain macrophages and fetal liver monocytes can generate bona fide SALL1+ microglia. Immunity 58, 1269–1288.e12 (2025).
Xu, H. et al. The choroid plexus synergizes with immune cells during neuroinflammation. Cell 187, 4946–4963.e17 (2024).
Cugurra, A. et al. Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science 373, eabf7844 (2021).
Chen, Y. et al. Macrophage-derived CTSS drives the age-dependent disruption of the blood–CSF barrier. Neuron 113, 1082–1097.e8 (2025).
Van Hove, H. et al. Interleukin-34-dependent perivascular macrophages promote vascular function in the brain. Immunity 58, 1289–1305.e8 (2025).
Butovsky, O. et al. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131–143 (2014).
Fixsen, B. R. et al. SALL1 enforces microglia-specific DNA binding and function of SMADs to establish microglia identity. Nat. Immunol. 24, 1188–1199 (2023).
Jordão, M. J. C. et al. Neuroimmunology: single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science 363, eaat7554 (2019).
Cui, J. et al. Inflammation of the embryonic choroid plexus barrier following maternal immune activation. Dev. Cell 55, 617–628.e6 (2020).
Sankowski, R. et al. Multiomic spatial landscape of innate immune cells at human central nervous system borders. Nat. Med. 30, 186–198 (2024).
Kearns, N. A. et al. Dissecting the human leptomeninges at single-cell resolution. Nat. Commun. 14, 7036 (2023).
Satpathy, A. T. et al. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat. Immunol. 14, 937–948 (2013).
Rojo, R. et al. Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. Nat. Commun. 10, 3215 (2019).
Yoshida, H. et al. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345, 442–444 (1990).
Yona, S. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91 (2013).
Goldmann, T. et al. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat. Neurosci. 16, 1618–1626 (2013).
Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 (2010).
Benz, C., Martins, V. C., Radtke, F. & Bleul, C. C. The stream of precursors that colonizes the thymus proceeds selectively through the early T lineage precursor stage of T cell development. J. Exp. Med. 205, 1187–1199 (2008).
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R. & Förster, I. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res 8, 265–277 (1999).
Levéen, P. et al. Induced disruption of the transforming growth factor beta type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable. Blood 100, 560–568 (2002).
Dranoff, G. et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 264, 713–716 (1994).
Kaiser, T. & Feng, G. Tmem119-EGFP and Tmem119-CreERT2 transgenic mice for labeling and manipulating microglia. eNeuro 6, 0448–18 (2019).
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e29 (2021).
van de Laar, L. et al. Yolk sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages. Immunity 44, 755–768 (2016).
Jin, S. et al. Inference and analysis of cell–cell communication using CellChat. Nat. Commun. 12, 1088 (2021).
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).
Van de Sande, B. et al. A scalable SCENIC workflow for single-cell gene regulatory network analysis. Nat. Protoc. 15, 2247–2276 (2020).


















Leave a Reply