Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor
Open accessAbstract
Astrocytes have important roles in the central nervous system (CNS) during health and disease. Through genome-wide analyses we detected a transcriptional response to type I interferons (IFN-Is) in astrocytes during experimental CNS autoimmunity and also in CNS lesions from patients with multiple sclerosis (MS). IFN-I signaling in astrocytes reduces inflammation and experimental autoimmune encephalomyelitis (EAE) disease scores via the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) and the suppressor of cytokine signaling 2 (SOCS2). The anti-inflammatory effects of nasally administered interferon (IFN)-β are partly mediated by AHR. Dietary tryptophan is metabolized by the gut microbiota into AHR agonists that have an effect on astrocytes to limit CNS inflammation. EAE scores were increased following ampicillin treatment during the recovery phase, and CNS inflammation was reduced in antibiotic-treated mice by supplementation with the tryptophan metabolites indole, indoxyl-3-sulfate, indole-3-propionic acid and indole-3-aldehyde, or the bacterial enzyme tryptophanase. In individuals with MS, the circulating levels of AHR agonists were decreased. These findings suggest that IFN-Is produced in the CNS function in combination with metabolites derived from dietary tryptophan by the gut flora to activate AHR signaling in astrocytes and suppress CNS inflammation.
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AHR activation suppresses NF-κB signaling and inhibits CNS inflammation in experimental autoimmune encephalomyelitis mouse models of multiple sclerosis.
“The AHR activation suppresses NF-κB signaling and inhibits CNS inflammation in experimental autoimmune encephalomyelitis (EAE) mouse models of multiple sclerosis.247,248”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [248]
IPA has proven neuroprotective properties.
“Of note, IPA, a molecule with proven neuroprotective properties (29), was enriched in feces from SAE-resistant mice.”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [29]
IPA may control microglia-activated inflammation through a mechanism mediated by AhR.
“Recent studies suggest that IPA may control microglia-activated inflammation through a mechanism mediated by AhR (29, 37).”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [29]
In the present study, IPA has a beneficial role in SAE, related to its anti-inflammatory effects.
“Consistent with previous findings (29, 32), we also observed a beneficial role for IPA in SAE, which was related to its anti-inflammatory effects.”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [29]
IPA has a protective effect against neuronal inflammation.
“These studies indicate the protective effect of IPA against neuronal inflammation, which prompted us to select IPA from the metabolites enriched in SER feces as a possible protective substance against SAE.”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [29]
Supplementation with the microbial metabolite IPA reduces neuroinflammation in mice with encephalomyelitis.
“In addition, supplementation with the microbial metabolite IPA was shown to reduce neuroinflammation in mice with encephalomyelitis (29).”
From Sepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice (2022) · cites this paper as [29]
The altered microbiota of patients could transfer the disease from a human host to a mouse host.
“Of extreme relevance, the altered microbiota of patients could transfer the disease from a human host to a mouse host (113, 116–120).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [118]
Treating mice with antibiotics or feeding them a tryptophan-deficient diet during the recovery phase of experimental autoimmune encephalomyelitis worsened the experimental autoimmune encephalomyelitis scores.
“Firstly, they showed that treating mice with antibiotics or feeding them with a Trp-deficient diet during the recovery phase of the EAE model worsened the EAE scores (118).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [118]
Aryl hydrocarbon receptor agonists act via a direct effect on astrocytes to limit CNS inflammation during experimental autoimmune encephalomyelitis.
“In conclusion, they suggested a mode of action of Ahr agonists, via a direct effect on astrocytes to limit CNS inflammation during EAE (118).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [118]
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Cites
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 11,930 · see citing works
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549 · see citing works
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413 · see citing works
Regulation of type I interferon responses
Ivashkiv, L. B., & Donlin, L. T. (2013) · Nature reviews. Immunology · doi:10.1038/nri3581 · Cited by 3,311 · see citing works
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
Yona, S., Kim, K.-W., Wolf, Y., Mildner, A., Varol, D., Breker, M., Strauss-Ayali, D., Viukov, S., Guilliams, M., Misharin, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.12.001 · Cited by 3,245 · see citing works
Self-citationMetabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites
Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., & Siuzdak, G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812874106 · Cited by 2,677 · see citing works
Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.003 · Cited by 2,614 · see citing works
Development, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452 · see citing works
The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide
Viaud, S., Saccheri, F., Mignot, G., Yamazaki, T., Daillère, R., Hannani, D., Enot, D. P., Pfirschke, C., Engblom, C., Pittet, M. J., et al. (2013) · Science · doi:10.1126/science.1240537 · Cited by 2,050 · see citing works
An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al. (2011) · Nature · doi:10.1038/nature10491 · Cited by 1,898 · see citing works
Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor
Quintana, F. J., Basso, A. S., Iglesias, A. H., Korn, T., Farez, M. F., Bettelli, E., Caccamo, M., Oukka, M., & Weiner, H. L. (2008) · Nature · doi:10.1038/nature06880 · Cited by 1,865 · see citing works
Self-citationThe aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
Veldhoen, M., Hirota, K., Westendorf, A. M., Buer, J., Dumoutier, L., Renauld, J.-C., & Stockinger, B. (2008) · Nature · doi:10.1038/nature06881 · Cited by 1,634 · see citing works
Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
Chung, W.-S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., Joung, J., Foo, L. C., Thompson, A., Chen, C., et al. (2013) · Nature · doi:10.1038/nature12776 · Cited by 1,377 · cited 1× · see citing works
“pSOCS:AhR(1) forward, 5′CCAGCTCCCTACCTGTTTGA-3′, and reverse, 5′-GGAATGGAGCGGACAGGA-3′; pSOCS2:AhR(2) forward, 5′-ATGAGTCAACACGTCCCAGA-3′, and reverse, 5′CTGCACACTCTCGTTTTGGG-3′, pSOCS2:AhR(3), forward, 5′TGGCAAAGTCTCTCGCAGA-3′, and reverse, 5′-TGCTCGGGGTTAAATGGTAC-3′.”
Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis
Lee, Y. K., Menezes, J. S., Umesaki, Y., & Mazmanian, S. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000082107 · Cited by 1,323 · see citing works
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
Berer, K., Mues, M., Koutrolos, M., Rasbi, Z. A., Boziki, M., Johner, C., Wekerle, H., & Krishnamoorthy, G. (2011) · Nature · doi:10.1038/nature10554 · Cited by 1,251 · see citing works
Diversity of astrocyte functions and phenotypes in neural circuits
Khakh, B. S., & Sofroniew, M. V. (2015) · Nature Neuroscience · doi:10.1038/nn.4043 · Cited by 1,239 · see citing works
Astrocyte barriers to neurotoxic inflammation
Sofroniew, M. V. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3898 · Cited by 1,202 · see citing works
Interferons at age 50: past, current and future impact on biomedicine
Borden, E. C., Sen, G. C., Uze, G., Silverman, R. H., Ransohoff, R. M., Foster, G. R., & Stark, G. R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2422 · Cited by 1,154 · see citing works
Th17 cell induction by adhesion of microbes to intestinal epithelial cells
Atarashi, K., Tanoue, T., Ando, M., Kamada, N., Nagano, Y., Narushima, S., Suda, W., Imaoka, A., Setoyama, H., Nagamori, T., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.058 · Cited by 1,071 · see citing works
The aryl hydrocarbon receptor: multitasking in the immune system
Stockinger, B., Meglio, P. D., Gialitakis, M., & Duarte, J. H. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120245 · Cited by 909 · see citing works
The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence
Alvarez, J. I., Dodelet-Devillers, A., Kebir, H., Ifergan, I., Fabre, P. J., Terouz, S., Sabbagh, M., Wosik, K., Bourbonnière, L., Bernard, M., et al. (2011) · Science · doi:10.1126/science.1206936 · Cited by 845 · see citing works
Self-citationExogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation
Li, Y., Innocentin, S., Withers, D. R., Roberts, N. A., Gallagher, A., Grigorieva, E. F., Wilhelm, C., & Veldhoen, M. (2011) · Cell · doi:10.1016/j.cell.2011.09.025 · Cited by 816 · see citing works
Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors
Allen, N. J., Bennett, M. L., Foo, L. C., Wang, G. X., Chakraborty, C., Smith, S. J., & Barres, B. A. (2012) · Nature · doi:10.1038/nature11059 · Cited by 764 · see citing works
TLR signaling tailors innate immune responses in human microglia and astrocytes
Jack, C. S., Arbour, N., Manusow, J., Montgrain, V., Blain, M., McCrea, E., Shapiro, A., & Antel, J. P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4320 · Cited by 734 · cited 1× · see citing works
“Human fetal astrocytes were isolated as previously described 11,63 from human CNS tissue from fetuses at 17–23 weeks of gestation obtained from the Human Fetal Tissue Repository (Albert Einstein College of Medicine) following Canadian Institutes of Health Research– approved guidelines.”
Apetoh, L., Quintana, F. J., Pot, C., Joller, N., Xiao, S., Kumar, D., Burns, E. J., Sherr, D. H., Weiner, H. L., & Kuchroo, V. K. (2010) · Nature Immunology · doi:10.1038/ni.1912 · Cited by 725 · see citing works
Self-citationAryl hydrocarbon receptor control of a disease tolerance defence pathway
Bessede, A., Gargaro, M., Pallotta, M. T., Matino, D., Servillo, G., Brunacci, C., Bicciato, S., Mazza, E. M. C., Macchiarulo, A., Vacca, C., et al. (2014) · Nature · doi:10.1038/nature13323 · Cited by 676 · see citing works
Heterogeneity of CNS myeloid cells and their roles in neurodegeneration
Prinz, M., Priller, J., Sisodia, S. S., & Ransohoff, R. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2923 · Cited by 674 · see citing works
Monteleone, I., Rizzo, A., Sarra, M., Sica, G., Sileri, P., Biancone, L., MacDonald, T. T., Pallone, F., & Monteleone, G. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.007 · Cited by 656 · see citing works
Aging-induced type I interferon response at the choroid plexus negatively affects brain function
Baruch, K., Deczkowska, A., David, E., Castellano, J. M., Miller, O., Kertser, A., Berkutzki, T., Barnett-Itzhaki, Z., Bezalel, D., Wyss-Coray, T., et al. (2014) · Science · doi:10.1126/science.1252945 · Cited by 615 · see citing works
Axtell, R., de Jong, B. D., Boniface, K., van der Voort, L. F., Bhat, R., Sarno, P. D., Naves, R., Han, M. H., Zhong, F., Castellanos, J. G., et al. (2010) · Nature Medicine · doi:10.1038/nm.2110 · Cited by 556 · see citing works
Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair
Tsai, H.-H., Li, H., Fuentealba, L., Molofsky, A., Taveira-Marques, R., Zhuang, H., Tenney, A., Murnen, A. T., Fancy, S., Merkle, F., et al. (2012) · Science · doi:10.1126/science.1222381 · Cited by 509 · see citing works
Gandhi, R., Kumar, D., Burns, E. J., Nadeau, M., Dake, B., Laroni, A., Kozoriz, D., Weiner, H. L., & Quintana, F. J. (2010) · Nature Immunology · doi:10.1038/ni.1915 · Cited by 479 · see citing works
Self-citationRegulation of astrocyte activation by glycolipids drives chronic CNS inflammation
Mayo, L., Trauger, S. A., Blain, M., Nadeau, M., Patel, B., Alvarez, J. I., Mascanfroni, I. D., Yeste, A., Kivisäkk, P., Kallas, K., et al. (2014) · Nature Medicine · doi:10.1038/nm.3681 · Cited by 472 · see citing works
Self-citationType I interferon responses in rhesus macaques prevent SIV infection and slow disease progression
Utay, N. S., Bosinger, S. E., Estes, J. D., Zhu, R. T., Tharp, G. K., Boritz, E., Levin, D., Wijeyesinghe, S., Nganou‐Makamdop, K., Prete, G. Q. D., et al. (2014) · Nature · doi:10.1038/nature13554 · Cited by 458 · see citing works
Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-α
Mascanfroni, I. D., Takenaka, M. C., Yeste, A., Patel, B., Wu, Y., Kenison, J. E., Siddiqui, S., Basso, A. S., Otterbein, L. E., Pardoll, D. M., et al. (2015) · Nature Medicine · doi:10.1038/nm.3868 · Cited by 441 · see citing works
Self-citationQuintana, F. J., Murugaiyan, G., Farez, M., Mitsdoerffer, M., Tukpah, A.-M. C., Burns, E. J., & Weiner, H. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009201107 · Cited by 430 · see citing works
Self-citationSuppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin
Shao, W., Zhang, S., Tang, M., Zhang, X., Zhou, Z., Yin, Y., Zhou, Q., Huang, Y., Liu, Y., Wawrousek, E. F., et al. (2012) · Nature · doi:10.1038/nature11748 · Cited by 418 · see citing works
Glial cells in the enteric nervous system contain glial fibrillary acidic protein
Jessen, K. R., & Mirsky, R. (1980) · Nature · doi:10.1038/286736a0 · Cited by 406 · see citing works
Prinz, M., Schmidt, H., Mildner, A., Knobeloch, K., Hanisch, U., Raasch, J., Merkler, D., Detje, C. N., Gutcher, I., Mages, J., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.011 · Cited by 387 · see citing works
Self-citationOchoa-Repáraz, J., Mielcarz, D. W., Ditrio, L. E., Burroughs, A. R., Begum-Haque, S., Dasgupta, S., Kasper, D. L., & Kasper, L. H. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001443 · Cited by 367 · see citing works
Aryl Hydrocarbon Receptor Control of Adaptive Immunity
Quintana, F. J., & Sherr, D. H. (2013) · Pharmacological Reviews · doi:10.1124/pr.113.007823 · Cited by 336 · see citing works
Self-citationSchroeder, J. C., DiNatale, B. C., Murray, I. A., Flaveny, C. A., Liu, Q., Laurenzana, E. M., Lin, J.-M., Strom, S. C., Omiecinski, C. J., Amin, S., et al. (2009) · Biochemistry · doi:10.1021/bi901786x · Cited by 330 · see citing works
Mascanfroni, I. D., Yeste, A., Vieira, S. M., Burns, E. J., Patel, B., Sloma, I., Wu, Y., Mayo, L., Ben‐Hamo, R., Efroni, S., et al. (2013) · Nature Immunology · doi:10.1038/ni.2695 · Cited by 328 · see citing works
Self-citationInterferon Beta Treatment in Neuromyelitis Optica
Palace, J. A., Leite, M. I., Nairne, A., & Vincent, A. C. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.188 · Cited by 323 · see citing works
Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses
Farez, M. F., Mascanfroni, I. D., Méndez-Huergo, S. P., Yeste, A., Murugaiyan, G., Garo, L. P., Balbuena Aguirre, M. E., Patel, B., Ysrraelit, M. C., Zhu, C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.025 · Cited by 318 · see citing works
Astrocyte-encoded positional cues maintain sensorimotor circuit integrity
Molofsky, A. V., Kelley, K. W., Tsai, H., Redmond, S., Chang, S., Madireddy, L., Chan, J. R., Baranzini, S. E., Ullian, E. M., & Rowitch, D. H. (2014) · Nature · doi:10.1038/nature13161 · Cited by 316 · see citing works
Fitzgerald, D. C., Ćirić, B., Touil, T., Harle, H., Grammatikopolou, J., Sarma, J. D., Gran, B., Zhang, G., & Rostami, A. M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.5.3268 · Cited by 307 · see citing works
Yeste, A., Nadeau, M., Burns, E. J., Weiner, H. L., & Quintana, F. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120611109 · Cited by 303 · see citing works
Self-citationRoss, T. M., Martinez, P. M., Renner, J. C., Thorne, R. G., Hanson, L. R., & Frey, W. H. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.02.011 · Cited by 242 · see citing works
Reproducibility of Metabolomic Profiles among Men and Women in 2 Large Cohort Studies
Townsend, M. K., Clish, C. B., Kraft, P., Wu, C. H., Souza, A. L., Deik, A., Tworoger, S. S., & Wolpin, B. M. (2013) · Clinical Chemistry · doi:10.1373/clinchem.2012.199133 · Cited by 237 · see citing works
Self-citationUSP18 lack in microglia causes destructive interferonopathy of the mouse brain
Goldmann, T., Zeller, N., Raasch, J., Kierdorf, K., Frenzel, K., Ketscher, L., Basters, A., Staszewski, O., Brendecke, S. M., Spiess, A., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490791 · Cited by 223 · see citing works
Self-citationLack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson’s Disease-like Dementia
Ejlerskov, P., Hultberg, J. G., Wang, J., Carlsson, R., Ambjørn, M., Kuss, M., Liu, Y., Porcu, G., Kolkova, K., Friis Rundsten, C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.069 · Cited by 211 · see citing works
Self-citationLoo, G., Lorenzi, R. D., Schmidt, H., Huth, M., Mildner, A., Schmidt‐Supprian, M., Lassmann, H., Prinz, M., & Pasparakis, M. (2006) · Nature Immunology · doi:10.1038/ni1372 · Cited by 197 · see citing works
Self-citationMechanisms of white matter damage in multiple sclerosis
Lassmann, H. (2014) · Glia · doi:10.1002/glia.22597 · Cited by 191 · see citing works
Kim, R. Y., Hoffman, A., Itoh, N., Ao, Y., Spence, R. D., Sofroniew, M. V., & Voskuhl, R. R. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.06.009 · Cited by 178 · see citing works
Nuclear factor kappa B (NF-κB) in multiple sclerosis pathology
Guire, C. M., Prinz, M., Beyaert, R., & Loo, G. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.08.001 · Cited by 154 · see citing works
Self-citationAlvarez, J. I., Saint-Laurent, O., Godschalk, A., Terouz, S., Briels, C., Larouche, S., Bourbonnière, L., Larochelle, C., & Prat, A. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.09.016 · Cited by 150 · see citing works
Self-citationThe glial cell response is an essential component of hypoxia-induced erythropoiesis in mice
Weidemann, A., Kerdiles, Y. M., Knaup, K. X., Rafie, C. A., Boutin, A. T., Stockmann, C., Takeda, N., Scadeng, M., Shih, A. Y., Haase, V. H., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39378 · Cited by 100 · see citing works
CNS-specific Therapy for Ongoing EAE by Silencing IL-17 Pathway in Astrocytes
Yan, Y., Ding, X., Li, K., Ćirić, B., Wu, S., Xu, H., Gran, B., Rostami, A. M., & Zhang, G. (2012) · Molecular Therapy · doi:10.1038/mt.2012.12 · Cited by 88 · see citing works
Zadjali, F., Santana‐Farré, R., Vesterlund, M., Carow, B., de Mirecki-Garrido, M., Hernández, I., Flodström‐Tullberg, M., Parini, P., Rottenberg, M. E., Norstedt, G., et al. (2012) · The FASEB Journal · doi:10.1096/fj.12-205583 · Cited by 71 · see citing works
Khorooshi, R., Mørch, M. T., Holm, T. H., Berg, C. T., Dieu, R. S., Dræby, D., Issazadeh‐Navikas, S., Weiß, S., Lienenklaus, S., & Owens, T. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1418-z · Cited by 69 · see citing works
Cytosolic RIG-I–like helicases act as negative regulators of sterile inflammation in the CNS
Dann, A., Poeck, H., Croxford, A. L., Gaupp, S., Kierdorf, K., Knust, M., Pfeifer, D., Maihöfer, C., Endres, S., Kalinke, U., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2964 · Cited by 64 · see citing works
Self-citation2,3,7,8-Tetrachlorodibenzo-p-dioxin Induces Suppressor of Cytokine Signaling 2 in Murine B Cells
Boverhof, D. R., Tam, E., Harney, A. S., Crawford, R. B., Kaminski, N. E., & Zacharewski, T. R. (2004) · Molecular Pharmacology · doi:10.1124/mol.104.002915 · Cited by 52 · see citing works
Building up the blood-brain barrier
Rieckmann, P., & Engelhardt, B. (2003) · Nature Medicine · doi:10.1038/nm0703-828 · Cited by 32 · see citing works
New pieces in the puzzle: How does interferon‐β really work in multiple sclerosis?
Mitsdoerffer, M., & Kuchroo, V. K. (2009) · Annals of Neurology · doi:10.1002/ana.21722 · Cited by 22 · see citing works
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Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F., & Opitz, C. A. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0016-5 · Cited by 1,586 · see citing works
Salt-responsive gut commensal modulates TH17 axis and disease
Wilck, N., Matus, M. G., Kearney, S. M., Olesen, S. W., Forslund, K., Bartolomaeus, H., Haase, S., Mähler, A., Balogh, A., Markó, L., et al. (2017) · Nature · doi:10.1038/nature24628 · Cited by 1,310 · see citing works
Rothhammer, V., & Quintana, F. J. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0125-8 · Cited by 1,197 · see citing works
Self-citationMicrobiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
Microglial control of astrocytes in response to microbial metabolites
Rothhammer, V., Borucki, D. M., Tjon, E. C., Takenaka, M. C., Chao, C.-C., Ardura-Fabregat, A., de Lima, K. A., Gutiérrez-Vázquez, C., Hewson, P., Staszewski, O., et al. (2018) · Nature · doi:10.1038/s41586-018-0119-x · Cited by 1,051 · see citing works
Self-citationGut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain
Gao, K., Mu, C.-L., Farzi, A., & Zhu, W.-Y. (2020) · Advances in Nutrition · doi:10.1093/advances/nmz127 · Cited by 1,029 · see citing works
Regulation of the immune response by the aryl hydrocarbon receptor
Gutiérrez-Vázquez, C., & Quintana, F. J. (2018) · Immunity · doi:10.1016/j.immuni.2017.12.012 · Cited by 985 · see citing works
Self-citationBerer, K., Gerdes, L. A., Cekanaviciute, E., Jia, X., Xiao, L., Xia, Z., Liu, C., Klotz, L., Stauffer, U., Baranzini, S. E., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1711233114 · Cited by 933 · see citing works
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876 · see citing works
“…Candida albicans; exacerbated DSS-induced colitis; and even altered susceptibility to experimental autoimmune encephalomyelitis (EAE) (Kiss et al., 2011; Lee et al., 2011; Li et al., 2011; Qiu et al., 2012; Rothhammer et al., 2016; Shi et al., 2007; Veldhoen et al., 2008; Zelante et al., 2013).”
BackgroundThe gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
Rutsch, A., Kantsjö, J. B., & Ronchi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604179 · Cited by 821 · see citing works
Hezaveh, K., Shinde, R. S., Klötgen, A., Halaby, M. J., Lamorte, S., Ciudad, M. T., Quevedo, R., Neufeld, L., Liu, Z. Q., Jin, R., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.01.006 · Cited by 746 · see citing works
Kynurenine pathway metabolism and the microbiota-gut-brain axis
Kennedy, P. J., Cryan, J. F., Dinan, T. G., & Clarke, G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.07.002 · Cited by 724 · see citing works
Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor
Scott, S. A., Fu, J., & Chang, P. V. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2000047117 · Cited by 696 · see citing works
Function and therapeutic value of astrocytes in neurological diseases
Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Self-citationThe gut microbiome and liver cancer: mechanisms and clinical translation
Yu, L.-X., & Schwabe, R. F. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.72 · Cited by 634 · see citing works
Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation
Prinz, M., Masuda, T., Wheeler, M. A., & Quintana, F. J. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-110159 · Cited by 584 · see citing works
Self-citationThe multiple pathways to autoimmunity
Theofilopoulos, A. N., Kono, D. H., & Baccala, R. (2017) · Nature Immunology · doi:10.1038/ni.3731 · Cited by 590 · see citing works
The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.10.002 · Cited by 555 · see citing works
Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39
Takenaka, M. C., Gabriely, G., Rothhammer, V., Mascanfroni, I. D., Wheeler, M. A., Chao, C.-C., Gutiérrez-Vázquez, C., Kenison, J., Tjon, E. C., Barroso, A., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0370-y · Cited by 517 · see citing works
Self-citationThe role of inflammation and the gut microbiome in depression and anxiety
Peirce, J. M., & Alviña, K. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24476 · Cited by 466 · see citing works
Gut microbiota and the neuroendocrine system
Farzi, A., Fröhlich, E. E., & Holzer, P. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0600-5 · Cited by 478 · see citing works
Microbiota-derived metabolites as drivers of gut–brain communication
Ahmed, H., Leyrolle, Q., Koistinen, V., Kärkkäinen, O., Layé, S., Delzenne, N., & Hanhineva, K. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2102878 · Cited by 462 · see citing works
Peripheral and central immune system crosstalk in Alzheimer disease — a research prospectus
Bettcher, B. M., Tansey, M. G., Dorothée, G., & Heneka, M. T. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00549-x · Cited by 427 · see citing works
The progress of gut microbiome research related to brain disorders
Zhu, S., Jiang, Y., Xu, K., Cui, M., Ye, W., Zhao, G., Jin, L., & Chen, X. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1705-z · Cited by 419 · see citing works
Gut microbial molecules in behavioural and neurodegenerative conditions
Needham, B. D., Kaddurah-Daouk, R., & Mazmanian, S. K. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-00381-0 · Cited by 379 · see citing works
The immunology of multiple sclerosis
Attfield, K. E., Jensen, L. T., Kaufmann, M., Friese, M. A., & Fugger, L. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00718-z · Cited by 380 · see citing works
Microbiome-modulated metabolites at the interface of host immunity
Blacher, E., Levy, M., Tatirovsky, E., & Elinav, E. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601247 · Cited by 354 · see citing works
The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology
Doifode, T., Giridharan, V. V., Generoso, J. S., Bhatti, G., Collodel, A., Schulz, P. E., Forlenza, O. V., & Barichello, T. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2020.105314 · Cited by 347 · see citing works
Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes
Sanmarco, L. M., Wheeler, M. A., Gutiérrez-Vázquez, C., Polonio, C. M., Linnerbauer, M., Pinho-Ribeiro, F. A., Li, Z., Giovannoni, F., Batterman, K. V., Scalisi, G., et al. (2021) · Nature · doi:10.1038/s41586-020-03116-4 · Cited by 331 · see citing works
Self-citationZhu, F., Guo, R., Wang, W., Ju, Y., Wang, Q., Ma, Q., Sun, Q., Fan, Y., Xie, Y., Yang, Z., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0475-4 · Cited by 323 · see citing works
Heiss, C. N., & Olofsson, L. E. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12684 · Cited by 304 · see citing works
Irritable bowel syndrome: a gut microbiota-related disorder?
Bhattarai, Y., Muniz Pedrogo, D. A., & Kashyap, P. C. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00338.2016 · Cited by 294 · see citing works
Immune cells and CNS physiology: Microglia and beyond
Norris, G. T., & Kipnis, J. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180199 · Cited by 274 · see citing works
The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored
Chandra, S., Sisodia, S. S., & Vassar, R. J. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00595-7 · Cited by 278 · see citing works
Pellegrini, C., Antonioli, L., Colucci, R., Blandizzi, C., & Fornai, M. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1856-5 · Cited by 270 · see citing works
Choi, S.-C., Brown, J., Gong, M., Ge, Y., Zadeh, M., Li, W., Croker, B. P., Michailidis, G., Garrett, T. J., Mohamadzadeh, M., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax2220 · Cited by 266 · see citing works
Deczkowska, A., Matcovitch-Natan, O., Tsitsou-Kampeli, A., Ben-Hamo, S., Dvir-Szternfeld, R., Spinrad, A., Singer, O., David, E., Winter, D. R., Smith, L. K., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00769-0 · Cited by 260 · see citing works
Self-citationJaglin, M., Rhimi, M., Philippe, C., Pons, N., Bruneau, A., Goustard, B., Daugé, V., Maguin, E., Naudon, L., & Rabot, S. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00216 · Cited by 269 · see citing works
T cell responses in the central nervous system
Korn, T., & Kallies, A. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.144 · Cited by 268 · see citing works
Zhang, Y., Huang, R., Cheng, M., Wang, L., Chao, J., Li, J., Zheng, P., Xie, P., Zhang, Z., & Yao, H. (2019) · Microbiome · doi:10.1186/s40168-019-0733-3 · Cited by 263 · see citing works
Ceyzériat, K., Ben Haim, L., Denizot, A., Pommier, D., Matos, M., Guillemaud, O., Palomares, M.-A., Abjean, L., Petit, F., Gipchtein, P., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0606-1 · Cited by 256 · see citing works
Brambilla, R. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01980-7 · Cited by 246 · see citing works
Sun, J., Zhang, Y., Kong, Y., Ye, T., Yu, Q., Kumaran Satyanarayanan, S., Su, K.-P., & Liu, J. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2022.08.003 · Cited by 255 · see citing works
Impacts of microbiome metabolites on immune regulation and autoimmunity
Haase, S., Haghikia, A., Wilck, N., Müller, D. N., & Linker, R. A. (2018) · Immunology · doi:10.1111/imm.12933 · Cited by 239 · see citing works
The intestinal barrier in disorders of the central nervous system
Pellegrini, C., Fornai, M., D'Antongiovanni, V., Antonioli, L., Bernardini, N., & Derkinderen, P. (2023) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(22)00241-2 · Cited by 239 · see citing works
Gut reactions: how the blood-brain barrier connects the microbiome and the brain
Logsdon, A. F., Erickson, M. A., Rhea, E. M., Salameh, T. S., & Banks, W. A. (2018) · Experimental Biology and Medicine · doi:10.1177/1535370217743766 · Cited by 235 · see citing works
Wu, L., Han, Y., Zheng, Z., Peng, G., Liu, P., Yue, S., Zhu, S., Chen, J., Lv, H., Shao, L., et al. (2021) · Nutrients · doi:10.3390/nu13010228 · Cited by 227 · see citing works
Spiljar, M., Merkler, D., & Trajkovski, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01353 · Cited by 219 · see citing works
Microglia and Astrocytes in Disease: Dynamic Duo or Partners in Crime?
Liddelow, S. A., Marsh, S. E., & Stevens, B. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.07.006 · Cited by 226 · see citing works
The function of gut microbiota in immune-related neurological disorders: a review
Sittipo, P., Choi, J., Lee, S., & Lee, Y. K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02510-1 · Cited by 221 · see citing works
Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Connell, E., Le Gall, G., Pontifex, M. G., Sami, S., Cryan, J. F., Clarke, G., Müller, M., & Vauzour, D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00548-6 · Cited by 208 · see citing works
Chidambaram, S. B., Essa, M. M., Rathipriya, A. G., Bishir, M., Ray, B., Mahalakshmi, A. M., Tousif, A. H., Sakharkar, M. K., Kashyap, R. S., Friedland, R. P., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107988 · Cited by 204 · see citing works
Russo, E., Giudici, F., Fiorindi, C., Ficari, F., Scaringi, S., & Amedei, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02754 · Cited by 204 · see citing works
The role of the gut microbiota in multiple sclerosis
Correale, J., Hohlfeld, R., & Baranzini, S. E. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00697-8 · Cited by 207 · see citing works
Probiotic treatment reduces depressive-like behaviour in rats independently of diet
Abildgaard, A., Elfving, B., Hokland, M., Wegener, G., & Lund, S. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.02.014 · Cited by 196 · see citing works
Deciphering the Chemical Lexicon of Host–Gut Microbiota Interactions
Nicolas, G. R., & Chang, P. V. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.04.006 · Cited by 195 · see citing works
The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis
Freedman, S. N., Shahi, S. K., & Mangalam, A. K. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0588-x · Cited by 168 · see citing works
Pellegrini, C., Antonioli, L., Calderone, V., Colucci, R., Fornai, M., & Blandizzi, C. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101806 · Cited by 174 · see citing works
Arnoriaga-Rodríguez, M., Mayneris-Perxachs, J., Burokas, A., Contreras-Rodríguez, O., Blasco, G., Coll, C., Biarnés, C., Miranda-Olivos, R., Latorre, J., Moreno-Navarrete, J.-M., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.09.002 · Cited by 157 · see citing works
Investigation of probiotics in multiple sclerosis
Tankou, S. K., Regev, K., Healy, B. C., Cox, L. M., Tjon, E., Kivisakk, P., Vanande, I. P., Cook, S., Gandhi, R., Glanz, B., et al. (2018) · Multiple Sclerosis Journal · doi:10.1177/1352458517737390 · Cited by 156 · see citing works
Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR)
Seok, S.-H., Ma, Z.-X., Feltenberger, J. B., Chen, H., Chen, H., Scarlett, C., Lin, Z., Satyshur, K. A., Cortopassi, M., Jefcoate, C. R., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000631 · Cited by 157 · see citing works
The role of glial cells in multiple sclerosis disease progression
Healy, L. M., Stratton, J. A., Kuhlmann, T., & Antel, J. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00624-x · Cited by 152 · see citing works
Self-citationThe aryl hydrocarbon receptor and the gut–brain axis
Barroso, A., Mahler, J. V., Fonseca-Castro, P. H., & Quintana, F. J. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00585-5 · Cited by 152 · see citing works
Self-citationMurray, E., Sharma, R., Smith, K. B., Mar, K. D., Barve, R., Lukasik, M., Pirwani, A. F., Malette-Guyon, E., Lamba, S., Thomas, B. J., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.06.016 · Cited by 150 · see citing works
The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)
Boddy, S. L., Giovannelli, I., Sassani, M., Cooper-Knock, J., Snyder, M. P., Segal, E., Elinav, E., Barker, L. A., Shaw, P. J., & McDermott, C. J. (2021) · BMC Medicine · doi:10.1186/s12916-020-01885-3 · Cited by 127 · see citing works
Role of the intestinal microbiome, intestinal barrier and psychobiotics in depression
Trzeciak, P., & Herbet, M. (2021) · Nutrients · doi:10.3390/nu13030927 · Cited by 139 · see citing works
Grishanova, A. Y., & Perepechaeva, M. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126719 · Cited by 130 · see citing works
Food Fight: Role of Itaconate and Other Metabolites in Antimicrobial Defense
Luan, H. H., & Medzhitov, R. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.013 · Cited by 130 · see citing works
Spichak, S., Bastiaanssen, T. F. S., Berding, K., Vlckova, K., Clarke, G., Dinan, T. G., & Cryan, J. F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.044 · Cited by 127 · see citing works
The Gut-Brain Axis in Inflammatory Bowel Disease—Current and Future Perspectives
Günther, C., Rothhammer, V., Karow, M., Neurath, M., & Winner, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168870 · Cited by 123 · see citing works
Self-citationBloemendaal, M., Szopinska-Tokov, J., Belzer, C., Boverhoff, D., Papalini, S., Michels, F., van Hemert, S., Arias Vasquez, A., & Aarts, E. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01404-9 · Cited by 118 · see citing works
The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke
Winek, K., Dirnagl, U., & Meisel, A. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0475-x · Cited by 108 · see citing works
The Role of Cytokines in the Pathogenesis of Schizophrenia
Dawidowski, B., Górniak, A., Podwalski, P., Lebiecka, Z., Misiak, B., & Samochowiec, J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10173849 · Cited by 102 · see citing works
Habashy, K. J., Mansour, R., Moussalem, C., Sawaya, R., & Massaad, M. J. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01864-w · Cited by 95 · see citing works
Of microbes and minds: A narrative review on the second brain aging
Calvani, R., Picca, A., Lo Monaco, M. R., Landi, F., Bernabei, R., & Marzetti, E. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00053 · Cited by 92 · see citing works
Acute microglia ablation induces neurodegeneration in the somatosensory system
Rubino, S. J., Mayo, L., Wimmer, I., Siedler, V., Brunner, F., Hametner, S., Madi, A., Lanser, A., Moreira, T., Donnelly, D., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05929-4 · Cited by 91 · see citing works
Self-citationSepsis-Induced Gut Dysbiosis Mediates the Susceptibility to Sepsis-Associated Encephalopathy in Mice
Fang, H., Wang, Y., Deng, J., Zhang, H., Wu, Q., He, L., Xu, J., Shao, X., Ouyang, X., He, Z., et al. (2022) · mSystems · doi:10.1128/msystems.01399-21 · Cited by 87 · see citing works
“The aryl hydrocarbon receptor (AhR) has been shown to negatively regulate NLRP3 inflammasome activity (21).”
BackgroundResultInfluentialThe Gut Microbiome as a Regulator of the Neuroimmune Landscape
Yu, L. W., Agirman, G., & Hsiao, E. Y. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-014237 · Cited by 75 · see citing works
Xie, Y., Zou, X., Han, J., Zhang, Z., Feng, Z., Ouyang, Q., Hua, S., Liu, Z., Li, C., Cai, Y., et al. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114081 · Cited by 80 · see citing works
Guo, L., Xiao, P., Zhang, X., Yang, Y., Yang, M., Wang, T., Lu, H., Tian, H., Wang, H., & Liu, J. (2021) · Food & Function · doi:10.1039/d0fo02778b · Cited by 74 · see citing works
Brinkmann, V., Ale-Agha, N., Haendeler, J., & Ventura, N. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2019.01561 · Cited by 71 · see citing works
Borghi, M., Pariano, M., Solito, V., Puccetti, M., Bellet, M. M., Stincardini, C., Renga, G., Vacca, C., Sellitto, F., Mosci, P., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02364 · Cited by 63 · see citing works
Stachulski, A. V., Knausenberger, T. B.-A., Shah, S. N., Hoyles, L., & McArthur, S. (2023) · Tissue Barriers · doi:10.1080/21688370.2022.2073175 · Cited by 61 · see citing works
Chandra, S., Di Meco, A., Dodiya, H. B., Popovic, J., Cuddy, L. K., Weigle, I. Q., Zhang, X., Sadleir, K., Sisodia, S. S., & Vassar, R. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00635-2 · Cited by 58 · see citing works
Regulation of microglial physiology by the microbiota
Cook, J., & Prinz, M. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2125739 · Cited by 49 · see citing works
Self-citationTruyens, M., Lobatón, T., Ferrante, M., Bossuyt, P., Vermeire, S., Pouillon, L., Dewint, P., Cremer, A., Peeters, H., Lambrecht, G., et al. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.07.052 · Cited by 48 · see citing works
Gut microbiome and Alzheimer’s disease: What we know and what remains to be explored
Kapoor, B., Biswas, P., Gulati, M., Rani, P., & Gupta, R. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102570 · Cited by 46 · see citing works
Hormones, Metabolism and the Benefits of Exercise
(2017) · Research and Perspectives in Endocrine Interactions · doi:10.1007/978-3-319-72790-5 · Cited by 44 · see citing works
Tyagi, P., Tasleem, M., Prakash, S., & Chouhan, G. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109489 · Cited by 42 · see citing works
Franchini, A. M., Myers, J. R., Jin, G.-B., Shepherd, D. M., & Lawrence, B. P. (2019) · ImmunoHorizons · doi:10.4049/immunohorizons.1900004 · Cited by 23 · see citing works
Jia, X., Chen, Q., Zhang, Y., & Asakawa, T. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1296713 · Cited by 22 · see citing works
Gut microbiota in multiple sclerosis and animal models
Schumacher, S. M., Doyle, W. J., Hill, K., & Ochoa‐Repáraz, J. (2025) · The FEBS Journal · doi:10.1111/febs.17161 · Cited by 21 · see citing works
Lakosa, A., Rahimian, A., Tomasi, F., Marti, F., Reynolds, L. M., Tochon, L., David, V., Danckaert, A., Canonne, C., Tahraoui, S., et al. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01563-x · Cited by 10 · see citing works
- Authors
- Rothhammer, V., Mascanfroni, I. D., Bunse, L., Takenaka, M. C., Kenison, J. E., Mayo, L., Chao, C.-C., Patel, B., Yan, R., Blain, M., Alvarez, J. I., Kébir, H., Anandasabapathy, N., Izquierdo, G., Jung, S., Obholzer, N., Pochet, N., Clish, C. B., Prinz, M., Prat, A., Antel, J., & Quintana, F. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Montreal Neurological Institute and Hospital (CA)
- University of Pennsylvania (US)
- Centre Hospitalier de l’Université de Montréal (CA)
- Universidad de Sevilla (ES)
- Weizmann Institute of Science (IL)
- Broad Institute (US)
- University of Freiburg (DE)
- Corresponding author
- Quintana, Francisco J
- ORCID
- Venue
- Nature Medicine
- Published
- 2016-05-09
- Volume
- 22
- Issue
- 6
- Pages
- 586-597
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4899206
- OpenAlex
- W2345604850
- Cited by
- 1,559
- References
- 65
- Citations by year
- 2026: 168 · 2025: 190 · 2024: 192 · 2023: 208 · 2022: 200 · 2021: 164 · 2020: 147 · 2019: 104 · 2018: 96 · 2017: 68 · 2016: 20
- FWCI
- 32.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute of Allergy and Infectious Diseases (R00AI075285, K99AI075285, R01AI093903, R56AI093903, R01AI126880)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- type I interferon, aryl hydrocarbon receptor, astrocytes, neuroinflammation, multiple sclerosis, experimental autoimmune encephalomyelitis, tryptophan metabolites, gut microbiota, SOCS2, interferon-beta, indole-3-propionic acid, indole-3-carboxaldehyde, tryptophanase, dietary tryptophan, central nervous system autoimmunity
- MeSH terms
- Gastrointestinal Microbiome, Animals, Astrocytes, Central Nervous System, Chromatography, High Pressure Liquid, Encephalomyelitis, Autoimmune, Experimental, Fluorescent Antibody Technique, Glial Fibrillary Acidic Protein, Humans, Indican, Indoles, Inflammation, Interferon Type I, Multiple Sclerosis, Serotonin, T-Lymphocytes, Tryptophan, Tryptophanase, Immunoblotting, Case-Control Studies, Polymerase Chain Reaction, Interferon-beta, Receptors, Aryl Hydrocarbon, Mice, Knockout, Chemokine CCL2, Gene Expression Profiling, Chromatin Immunoprecipitation, Cell Proliferation, STAT1 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice, Limosilactobacillus reuteri, Nitric Oxide Synthase Type II, Receptor, Interferon alpha-beta, Gene Knockdown Techniques, Optical Imaging, Myxovirus Resistance Proteins
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