Ito, M. et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature 565, 246–250 (2019).

Article  CAS  PubMed  Google Scholar 

Yshii, L. et al. Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation. Nat. Immunol. 23, 878–891 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pasciuto, E. et al. Microglia require CD4 T cells to complete the fetal-to-adult transition. Cell 182, 625–640.e624 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shen, Y. et al. CCR5 closes the temporal window for memory linking. Nature 606, 146–152 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nautiyal, K. M., Ribeiro, A. C., Pfaff, D. W. & Silver, R. Brain mast cells link the immune system to anxiety-like behavior. Proc. Natl Acad. Sci. USA 105, 18053–18057 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gaudenzio, N. et al. Different activation signals induce distinct mast cell degranulation strategies. J. Clin. Invest. 126, 3981–3998 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Sankowski, R. et al. Multiomic spatial landscape of innate immune cells at human central nervous system borders. Nat. Med. 30, 186–198 (2024).

Article  CAS  PubMed  Google Scholar 

Villeda, S. A. et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477, 90 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Villeda, S. A. et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat. Med. 20, 659 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fernández-Castañeda, A. et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell 185, 2452–2468 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Wälchli, T. et al. Single-cell atlas of the human brain vasculature across development, adulthood and disease. Nature 632, 603–613 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Wu, L. et al. Conditional knockout of IL-1R1 in endothelial cells attenuates seizures and neurodegeneration via inhibiting neuroinflammation mediated by Nrf2/HO-1/NLRP3 signaling in status epilepticus model. Mol. Neurobiol. 61, 4289–4303 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Nehmé, A. & Edelman, J. Dexamethasone inhibits high glucose-, TNF-α-, and IL-1β-induced secretion of inflammatory and angiogenic mediators from retinal microvascular pericytes. Invest. Ophthalmol. Vis. Sci. 49, 2030–2038 (2008).

Article  PubMed  Google Scholar 

Persidsky, Y. et al. Dysfunction of brain pericytes in chronic neuroinflammation. J. Cereb. Blood Flow. Metab. 36, 794–807 (2016).

Article  CAS  PubMed  Google Scholar 

Leaf, I. A. et al. Pericyte MyD88 and IRAK4 control inflammatory and fibrotic responses to tissue injury. J. Clin. Invest. 127, 321–334 (2017).

Article  PubMed  Google Scholar 

Duan, L. et al. PDGFRβ cells rapidly relay inflammatory signal from the circulatory system to neurons via chemokine CCL2. Neuron 100, 183–200.e188 (2018).

Article  CAS  PubMed  Google Scholar 

Ji, E. et al. The chemokine CCL2 promotes excitatory synaptic transmission in hippocampal neurons via GluA1 subunit trafficking. Neurosci. Bull. 40, 1649–1666 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guo, H. et al. CCL2 potentiates inflammation pain and related anxiety-like behavior through NMDA signaling in anterior cingulate cortex. Mol. Neurobiol. 61, 4976–4991 (2024).

Article  CAS  PubMed  Google Scholar 

Dror, E. et al. Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat. Immunol. 18, 283–292 (2017).

Article  CAS  PubMed  Google Scholar 

Leidmaa, E., Zimmer, A., Stein, V. & Gellner, A.-K. Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice. Preprint at bioRxiv https://doi.org/10.1101/2024.04.14.589405 (2024).

Gillespie, K. M. et al. The impact of free and added sugars on cognitive function: a systematic review and meta-analysis. Nutrients 16, 75 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Fetsko, A. R., Sebo, D. J., Budzynski, L. B., Scharbarth, A. & Taylor, M. R. IL-1β disrupts the initiation of blood-brain barrier development by inhibiting endothelial Wnt/β-catenin signaling. iScience 27, 109651 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu, X. et al. Cell-type-specific interleukin 1 receptor 1 signaling in the brain regulates distinct neuroimmune activities. Immunity 50, 317–333.e316 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Avital, A. et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus 13, 826–834 (2003).

Article  CAS  PubMed  Google Scholar 

Drieu, A. et al. Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Nature 611, 585–593 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kaplan, L., Chow, B. W. & Gu, C. Neuronal regulation of the blood–brain barrier and neurovascular coupling. Nat. Rev. Neurosci. 21, 416–432 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Somasundaram, V. et al. Inducible nitric oxide synthase-derived extracellular nitric oxide flux regulates proinflammatory responses at the single cell level. Redox Biol. 28, 101354 (2020).

Article  CAS  PubMed  Google Scholar 

Haruwaka, K. et al. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat. Commun. 10, 5816 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Belenichev, I. et al. Modulating nitric oxide: implications for cytotoxicity and cytoprotection. Antioxidants 13, 504 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pfau, S. J. et al. Characteristics of blood–brain barrier heterogeneity between brain regions revealed by profiling vascular and perivascular cells. Nat. Neurosci. 27, 1892–1903 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ghersi-Egea, J. F. et al. Molecular anatomy and functions of the choroidal blood–cerebrospinal fluid barrier in health and disease. Acta Neuropathol. 135, 337–361 (2018).

Article  CAS