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The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour

  • Jaschke, N. P. & Wang, A. Integrated control of leukocyte compartments as a feature of adaptive physiology. Immunity 58, 279–294 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

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

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pappalardo, J. L. et al. Transcriptomic and clonal characterization of T cells in the human central nervous system. Sci. Immunol. 5, eabb8786 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smolders, J. et al. Tissue-resident memory T cells populate the human brain. Nat. Commun. 9, 4593 (2018).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schnell, A. et al. Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity. Cell 184, 6281–6298 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Berer, K. et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479, 538–541 (2011).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Seki, D. et al. Aberrant gut–microbiota–immune–brain axis development in premature neonates with brain damage. Cell Host Microbe 29, 1558–1572 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, S. et al. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature 549, 528–532 (2017).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sampson, T. R. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469–1480 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Medawar, P. B. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br. J. Exp. Pathol. 29, 58–69 (1948).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carson, M. J., Doose, J. M., Melchior, B., Schmid, C. D. & Ploix, C. C. CNS immune privilege: hiding in plain sight. Immunol. Rev. 213, 48–65 (2006).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Radjavi, A., Smirnov, I. & Kipnis, J. Brain antigen-reactive CD4+T cells are sufficient to support learning behavior in mice with limited T cell repertoire. Brain Behav. Immun. 35, 58–63 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rattazzi, L. et al. CD4+ but not CD8+T cells revert the impaired emotional behavior of immunocompromised RAG-1-deficient mice. Transl. Psychiatry 3, e280 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Derecki, N. C. et al. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J. Exp. Med. 207, 1067–1080 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Filiano, A. J. et al. Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour. Nature 535, 425–429 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ribeiro, M. et al. Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short-term memory. Sci. Immunol. 4, eaay5199 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alves de Lima, K. et al. Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons. Nat. Immunol. 21, 1421–1429 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hindmarch, C. C. & Ferguson, A. V. Physiological roles for the subfornical organ: a dynamic transcriptome shaped by autonomic state. J. Physiol. 594, 1581–1589 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pulman, K. J., Fry, W. M., Cottrell, G. T. & Ferguson, A. V. The subfornical organ: a central target for circulating feeding signals. J. Neurosci. 26, 2022–2030 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Takahashi, Y., Smith, P., Ferguson, A. & Pittman, Q. J. Circumventricular organs and fever. Am. J. Physiol. 273, R1690–R1695 (1997).

    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, J. et al. Projections from subfornical organ to bed nucleus of the stria terminalis modulate inflammation-induced anxiety-like behaviors in mice. Sci. Adv. 10, eadp9413 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Omri, B. et al. CD4 expression in neurons of the central nervous system. Int. Immunol. 6, 377–385 (1994).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Collins, N. et al. The bone marrow protects and optimizes immunological memory during dietary restriction. Cell 178, 1088–1101 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res. 30, 492–506 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, B. et al. A high-fat diet increases gut microbiota biodiversity and energy expenditure due to nutrient difference. Nutrients 12, 3197 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Al Nabhani, Z. et al. A weaning reaction to microbiota is required for resistance to immunopathologies in the adult. Immunity 50, 1276–1288 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Morton, A. M. et al. Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut. Proc. Natl Acad. Sci. USA 111, 6696–6701 (2014).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Galván-Peña, S., Zhu, Y., Hanna, B. S., Mathis, D. & Benoist, C. A dynamic atlas of immunocyte migration from the gut. Sci. Immunol. 9, eadi0672 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Odoardi, F. et al. T cells become licensed in the lung to enter the central nervous system. Nature 488, 675–679 (2012).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Samuels, B. A. & Hen, R. in Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests Vol. II (ed. Gould, T. D.) 107–121 (Humana Press, 2011).

  • Kunis, G. et al. IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair. Brain 136, 3427–3440 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Zheng, Y. et al. Blocking the IFN-gamma signal in the choroid plexus confers resistance to experimental autoimmune encephalomyelitis. FASEB J. 37, e22833 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Szabo, S. J. et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655–669 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Szabo, S. J. et al. Distinct effects of T-bet in TH1 lineage commitment and IFN-γ production in CD4 and CD8 T cells. Science 295, 338–342 (2002).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, Y. et al. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med. 213, 667–675 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, S. et al. APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge. Cell Rep. 42, 112196 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lituma, P. J. et al. Altered synaptic connectivity and brain function in mice lacking microglial adapter protein Iba1. Proc. Natl Acad. Sci. USA 118, e2115539118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hong, S. et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712–716 (2016).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wójtowicz, S., Strosznajder, A. K., Jeżyna, M. & Strosznajder, J. B. The novel role of PPAR alpha in the brain: promising target in therapy of Alzheimer’s disease and other neurodegenerative disorders. Neurochem. Res. 45, 972–988 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clark, D. N. et al. Prolonged STAT1 activation in neurons drives a pathological transcriptional response. J. Neuroimmunol. 382, 578168 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clark, D. N. et al. Prolonged STAT1 signaling in neurons causes hyperactive behavior. Brain Behav. Immun. 124, 1–8 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Clark, D. N., Begg, L. R. & Filiano, A. J. Unique aspects of IFN-γ/STAT1 signaling in neurons. Immunol. Rev. 311, 187–204 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smith, B. C. et al. Astrocyte interferon-gamma signaling dampens inflammation during chronic central nervous system autoimmunity via PD-L1. J. Neuroinflammation 20, 234 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hindinger, C. et al. IFN-γ signaling to astrocytes protects from autoimmune mediated neurological disability. PLoS One 7, e42088 (2012).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clark, I. C. et al. Barcoded viral tracing of single-cell interactions in central nervous system inflammation. Science 372, eabf1230 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kantzer, C. G. et al. Anti-ACSA-2 defines a novel monoclonal antibody for prospective isolation of living neonatal and adult astrocytes. Glia 65, 990–1004 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Giedd, J. N., Castellanos, F. X., Rajapakse, J. C., Vaituzis, A. C. & Rapoport, J. L. Sexual dimorphism of the developing human brain. Prog. Neuropsychopharmacol. Biol. Psychiatry 21, 1185–1201 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rurak, G. M. et al. Sex differences in developmental patterns of neocortical astroglia: a mouse translatome database. Cell Rep. 38, 110310 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Barr, M. M., García, L. R. & Portman, D. S. Sexual dimorphism and sex differences in Caenorhabditis elegans neuronal development and behavior. Genetics 208, 909–935 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Unutmaz, D. et al. The primate lentiviral receptor Bonzo/STRL33 is coordinately regulated with CCR5 and its expression pattern is conserved between human and mouse. J. Immunol. 165, 3284–3292 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Oxenius, A., Bachmann, M. F., Zinkernagel, R. M. & Hengartner, H. Virus-specific MHC-class II-restricted TCR-transgenic mice: effects on humoral and cellular immune responses after viral infection. Eur. J. Immunol. 28, 390–400 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yang, Y. et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510, 152–156 (2014).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lodolce, J. P. et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 9, 669–676 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dufour, J. H. et al. IFN-γ-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J. Immunol. 168, 3195–3204 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Griswold, S. L., Sajja, K. C., Jang, C. W. & Behringer, R. R. Generation and characterization of iUBC-KikGR photoconvertible transgenic mice for live time-lapse imaging during development. Genesis 49, 591–598 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mombaerts, P. et al. Mutations in T-cell antigen receptor genes α and β block thymocyte development at different stages. Nature 360, 225–231 (1992).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Dalton, D. K. et al. Multiple defects of immune cell function in mice with disrupted interferon-γ genes. Science 259, 1739–1742 (1993).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Finotto, S. et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336–338 (2002).

    Article 
    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Haas, J. D. et al. Development of interleukin-17-producing γδ T cells is restricted to a functional embryonic wave. Immunity 37, 48–59 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee, S. H. et al. Identifying the initiating events of anti-Listeria responses using mice with conditional loss of IFN-γ receptor subunit 1 (IFNGR1). J. Immunol. 191, 4223–4234 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yona, S. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gregorian, C. et al. Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis. J. Neurosci. 29, 1874–1886 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tronche, F. et al. Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat. Genet. 23, 99–103 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Park, Y. G. et al. Protection of tissue physicochemical properties using polyfunctional crosslinkers. Nat. Biotechnol. 37, 73–83 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stoeckius, M. et al. Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics. Genome Biol. 19, 224 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Borcherding, N., Bormann, N. L. & Kraus, G. scRepertoire: an R-based toolkit for single-cell immune receptor analysis. F1000Res. 9, 47 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Street, K. et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Van den Berge, K. et al. Trajectory-based differential expression analysis for single-cell sequencing data. Nat. Commun. 11, 1201 (2020).

    Article 
    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qi, G., Mi, Y. & Yin, F. Characterizing brain metabolic function ex vivo with acute mouse slice punches. STAR Protoc. 2, 100559 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pennington, Z. T. et al. ezTrack: an open-source video analysis pipeline for the investigation of animal behavior. Sci. Rep. 9, 19979 (2019).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Favuzzi, E. et al. GABA-receptive microglia selectively sculpt developing inhibitory circuits. Cell 184, 4048–4063 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

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