Sekirov, I., Russell, S. L., Antunes, L. C. & Finlay, B. B. Gut microbiota in health and disease. Physiol. Rev. 90, 859–904 (2010).
Morgan, X. C. et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 13, R79 (2012).
Halfvarson, J. et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat. Microbiol. 2, 17004 (2017).
Wang, Y. & Kasper, L. H. The role of microbiome in central nervous system disorders. Brain Behav. Immun. 38, 1–12 (2014).
Belkaid, Y. & Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 157, 121–141 (2014).
Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).
Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012).
Honda, K. & Littman, D. R. The microbiota in adaptive immune homeostasis and disease. Nature 535, 75–84 (2016).
Kiner, E. et al. Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes. Nat. Immunol. 22, 216–228 (2021).
Hegazy, A. N. et al. Circulating and tissue-resident CD4+ T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology 153, 1320–1337.e1316 (2017).
Sano, T. et al. Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes. Cell Rep. 36, 109608 (2021).
Horai, R. et al. Microbiota-dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site. Immunity 43, 343–353 (2015).
Miyauchi, E. et al. Gut microorganisms act together to exacerbate inflammation in spinal cords. Nature 585, 102–106 (2020).
Blumershine, R. V. & Savage, D. C. Filamentous microbes indigenous to the murine small bowel: a scanning electron microscopic study of their morphology and attachment to the epithelium. Microb. Ecol. 4, 95–103 (1977).
Klaasen, H. L., Koopman, J. P., Poelma, F. G. & Beynen, A. C. Intestinal, segmented, filamentous bacteria. FEMS Microbiol. Rev. 8, 165–180 (1992).
Klaasen, H. L. et al. Intestinal, segmented, filamentous bacteria in a wide range of vertebrate species. Lab. Anim. 27, 141–150 (1993).
Yin, Y. et al. Comparative analysis of the distribution of segmented filamentous bacteria in humans, mice and chickens. ISME J. 7, 615–621 (2013).
Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).
Gaboriau-Routhiau, V. et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31, 677–689 (2009).
Yang, Y. et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510, 152–156 (2014).
Sano, T. et al. An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell 163, 381–393 (2015).
Wu, H. J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815–827 (2010).
Lee, Y. K., Menezes, J. S., Umesaki, Y. & Mazmanian, S. K. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc. Natl Acad. Sci. USA 108, 4615–4622 (2011).
Bradley, C. P. et al. Segmented filamentous bacteria provoke lung autoimmunity by inducing gut–lung axis Th17 cells expressing dual TCRs. Cell Host Microbe 22, 697–704.e694 (2017).
Powrie, F., Leach, M. W., Mauze, S., Caddle, L. B. & Coffman, R. L. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int. Immunol. 5, 1461–1471 (1993).
Morrissey, P. J., Charrier, K., Braddy, S., Liggitt, D. & Watson, J. D. CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. Disease development is prevented by cotransfer of purified CD4+ T cells. J. Exp. Med. 178, 237–244 (1993).
Mottet, C., Uhlig, H. H. & Powrie, F. Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J. Immunol. 170, 3939–3943 (2003).
Stepankova, R. et al. Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cells. Inflamm. Bowel Dis. 13, 1202–1211 (2007).
Britton, G. J. et al. Microbiotas from humans with inflammatory bowel disease alter the balance of gut Th17 and RORγt+ regulatory T cells and exacerbate colitis in mice. Immunity 50, 212–224.e214 (2019).
Chassaing, B. et al. Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation. PLoS ONE 7, e44328 (2012).
Guyenet, S. J. et al. A simple composite phenotype scoring system for evaluating mouse models of cerebellar ataxia. J. Vis. Exp. https://doi.org/10.3791/1787 (2010).
Rangachari, M. & Kuchroo, V. K. Using EAE to better understand principles of immune function and autoimmune pathology. J. Autoimmun. 45, 31–39 (2013).
Boniface, K. et al. Human Th17 cells comprise heterogeneous subsets including IFN-γ-producing cells with distinct properties from the Th1 lineage. J Immunol 185, 679–687 (2010).
Kebir, H. et al. Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis. Ann. Neurol. 66, 390–402 (2009).
He, X. et al. Dual receptor T cells extend the immune repertoire for foreign antigens. Nat. Immunol. 3, 127–134 (2002).
Elliott, J. I. & Altmann, D. M. Dual T cell receptor alpha chain T cells in autoimmunity. J. Exp. Med. 182, 953–959 (1995).
Fahey, J. R. et al. Antibiotic-associated manipulation of the gut microbiota and phenotypic restoration in NOD mice. Comp. Med. 67, 335–343 (2017).
Surh, C. D. & Sprent, J. Homeostasis of naive and memory T cells. Immunity 29, 848–862 (2008).
Gunther, C., Rothhammer, V., Karow, M., Neurath, M. & Winner, B. The gut–brain axis in inflammatory bowel disease—current and future perspectives. Int. J. Mol. Sci. 22, 8870 (2021).
Carloni, S. et al. Identification of a choroid plexus vascular barrier closing during intestinal inflammation. Science 374, 439–448 (2021).
Mickael, M. E. et al. RORγt-expressing pathogenic CD4+ T cells cause brain inflammation during chronic colitis. J. Immunol. 208, 2054–2066 (2022).
Parry, R. V. et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell. Biol. 25, 9543–9553 (2005).
Larkin, J. et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 23–34 (2015).
Kim, J. M., Rasmussen, J. P. & Rudensky, A. Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8, 191–197 (2007).
Wang, Y. et al. The transcription factors T-bet and Runx are required for the ontogeny of pathogenic interferon-γ-producing T helper 17 cells. Immunity 40, 355–366 (2014).
Langrish, C. L. et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233–240 (2005).
Ito, D. et al. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res. Mol. Brain Res. 57, 1–9 (1998).
Spangenberg, E. et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model. Nat. Commun. 10, 3758 (2019).
Zegarra-Ruiz, D. F. et al. Thymic development of gut-microbiota-specific T cells. Nature 594, 413–417 (2021).
Bettelli, E. et al. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J. Exp. Med. 197, 1073–1081 (2003).
Wagner, N. et al. Critical role for β7 integrins in formation of the gut-associated lymphoid tissue. Nature 382, 366–370 (1996).
Finotto, S. et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295, 336–338 (2002).
Dranoff, G. et al. Involvement of granulocyte-macrophage colony-stimulating factor in pulmonary homeostasis. Science 264, 713–716 (1994).
Lee, P. P. et al. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15, 763–774 (2001).
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).
Leonard, J. D. et al. Identification of natural regulatory T cell epitopes reveals convergence on a dominant autoantigen. Immunity 47, 107–117.e108 (2017).
Kanaan, A., Farahani, R., Douglas, R. M., Lamanna, J. C. & Haddad, G. G. Effect of chronic continuous or intermittent hypoxia and reoxygenation on cerebral capillary density and myelination. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R1105–R1114 (2006).
Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293–304 (2024).
Wendimu, M. Y. & Hooks, S. B. Microglia phenotypes in aging and neurodegenerative diseases. Cells 11, 2091 (2022).
Sano, T. Single-cell RNA-seq and TCR-seq datasets for the article: Intestinal inflammation promotes gut commensal-specific CD4 T cell to initiate molecular mimicry-mediated neuroinflammation [Data set]. Zenodo https://doi.org/10.5281/zenodo.15276655 (2025).