Cited by 1,457T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisGut microbiota and health

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Bile acid metabolites control TH17 and Treg cell differentiation

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Hang, Saiyu, Paik, Donggi, Yao, Lina, Kim, Eunha, Trinath, Jamma, Lu, Jingping, Ha, Soyoung, Nelson, Brandon N., Kelly, Samantha P., Wu, Lin, Zheng, Ye, Longman, Randy S., Rastinejad, Fraydoon, Devlin, A. Sloan, Krout, Michael R., Fischbach, Michael A., Littman, Dan R., Huh, Jun R.·2019·Nature

DOI 10.1038/s41586-019-1785-zPMC PMC6949019

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Abstract

Bile acids are abundant in the mammalian gut, where they undergo bacteria-mediated transformation to generate a large pool of bioactive molecules. Although bile acids are known to affect host metabolism, cancer progression and innate immunity, it is unknown whether they affect adaptive immune cells such as T helper cells that express IL-17a (T H 17 cells) or regulatory T cells (T reg cells). Here we screen a library of bile acid metabolites and identify two distinct derivatives of lithocholic acid (LCA), 3-oxoLCA and isoalloLCA, as T cell regulators in mice. 3-OxoLCA inhibited the differentiation of T H 17 cells by directly binding to the key transcription factor retinoid-related orphan receptor-γt (RORγt) and isoalloLCA increased the differentiation of T reg cells through the production of mitochondrial reactive oxygen species (mitoROS), which led to increased expression of FOXP3. The isoalloLCA-mediated enhancement of T reg cell differentiation required an intronic Foxp3 enhancer, the conserved noncoding sequence (CNS) 3; this represents a mode of action distinct from that of previously identified metabolites that increase T reg cell differentiation, which require CNS1. The administration of 3-oxoLCA and isoalloLCA to mice reduced T H 17 cell differentiation and increased T reg cell differentiation, respectively, in the intestinal lamina propria. Our data suggest mechanisms through which bile acid metabolites control host immune responses, by directly modulating the balance of T H 17 and T reg cells.

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Callahan, B. J., McMurdie, P. J., Rosen, M. J., Han, A. W., Johnson, A. J. A., & Holmes, S. P. (2016) · Nature Methods · doi:10.1038/nmeth.3869 · Cited by 35,698
Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2’s q2-feature-classifier plugin
Bokulich, N. A., Kaehler, B. D., Rideout, J. R., Dillon, M. R., Bolyen, E. K., Knight, R. D., Huttley, G. A., & Caporaso, J. G. (2018) · Microbiome · doi:10.1186/s40168-018-0470-z · Cited by 6,037
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., et al. (2013) · Nature · doi:10.1038/nature12726 · Cited by 4,838
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
Self-citation
Bile salt biotransformations by human intestinal bacteria
Ridlon, J. M., Kang, D.-J., & Hylemon, P. B. (2006) · Journal of Lipid Research · doi:10.1194/jlr.r500013-jlr200 · Cited by 2,829
Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile
Buffie, C. G., Bucci, V., Stein, R. R., McKenney, P. T., Ling, L., Gobourne, A., No, D., Liu, H., Kinnebrew, M., Viale, A., et al. (2015) · Nature · doi:10.1038/nature13828 · Cited by 1,872
Gut microbiome–mediated bile acid metabolism regulates liver cancer via NKT cells
Ma, C., Han, M., Heinrich, B., Fu, Q., Zhang, Q., Sandhu, M., Agdashian, D., Terabe, M., Berzofsky, J. A., Fako, V., et al. (2018) · Science · doi:10.1126/science.aan5931 · Cited by 1,508
Mitochondria are required for antigen-specific t cell activation through reactive oxygen species signaling
Sena, L. A., Li, S., Jairaman, A., Prakriya, M., Ezponda, T., Hildeman, D. A., Wang, C.-R., Schumacker, P. T., Licht, J. D., Perlman, H., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.10.020 · Cited by 1,338
Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments
Angelin, A., Gil‐de‐Gómez, L., Dahiya, S., Jiao, J., Guo, L., Levine, M. H., Wang, Z., Quinn, W. J., Kopinski, P. K., Wang, L., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.018 · Cited by 1,304
T cell metabolism drives immunity
Buck, M. D., O’Sullivan, D., & Pearce, E. L. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20151159 · Cited by 1,238

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Role and progression of bile acid metabolism in mediating Th17/Treg homeostasis in inflammatory bowel disease
Yue, S. R., Tan, Y. L., Gong, L., & Liao, F. (2026) · iScience · doi:10.1016/j.isci.2026.114961 · Cited by 5
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Development of non-alcoholic steatohepatitis is associated with gut microbiota but not with oxysterol enzymes CH25H, EBI2, or CYP7B1 in mice
Wyss, J., Raselli, T., Wyss, A., Telzerow, A., Rogler, G., Krupka, N., Yılmaz, B., Schmidt, T., & Misselwitz, B. (2024) · BMC Microbiology · doi:10.1186/s12866-024-03195-7 · Cited by 4
Regulation of MAIT cells through host-derived antigens
Ito, E., & Yamasaki, S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1424987 · Cited by 4
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Liu, K., Zhang, K., Yang, Y., Zong, Y., He, Z., Chen, W., Li, J., & Du, R. (2024) · Journal of Functional Foods · doi:10.1016/j.jff.2024.106637 · Cited by 4
Immunomodulatory effects of calorie restriction and its mimetics: A new potential therapeutic approach for autoimmune diseases
Sen, M. K., Liao, E., Ni, D., Ge, A., & Piccio, L. M. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100063 · Cited by 5
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Pre-diagnostic circulating bile acid concentrations and liver cancer risk: a nested case-control analysis of 12 cohorts
Watling, C. Z., Petrick, J. L., Graubard, B. I., Zhang, X., Barnett, M. J., Buring, J. E., Chen, Y., Eliassen, A. H., Gaziano, J. M., Hofmann, J. N., et al. (2025) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkaf086 · Cited by 4
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Yuan, Y., Hu, J., Lu, X., Han, H., Wang, M., Zhang, W., Yao, J., Li, Y., Lin, Z., Liang, C., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157409 · Cited by 4
Fructose intake driven glycolysis-ROS-EGFR axis specifically promotes the generation and pathogenicity of Th17 cells
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Chen, Y., Jia, B., Tong, X., Yin, S., Ni, W., Zhao, Q., Shi, J., & Li, J. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000864 · Cited by 5
From alpha diversity to zeitgebers: Functional implications and potential mechanisms linking the gut microbiome to sleep and circadian disruption (Part II)
Maki, K. A., Barb, J. J., Xu, S., Papneja, S., Alkhatib, J., Butera, G., & Wallen, G. R. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106609 · Cited by 5
Cross-kingdom microbial interactions in the gut during inflammatory bowel disease
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Biagioli, M., Giorgio, C. D., Marchianò, S., Sensini, B., Urbani, G., Giannelli, E., Lachi, G., Massa, C., Sette, M. R., Paniconi, F., et al. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2645125 · Cited by 4
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Wang, Q., Zhou, Z., Pang, L., Du, Y., Li, X., & Dai, L. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1802845 · Cited by 4
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Torres-Mayo, A., Liébana-García, R., Olivares, M., Pellón, A., Anguíta, J., & Sanz, Y. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2667610 · Cited by 5
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Jiang, Q., Zhu, G., Ma, X. C., Si, W., & Yang, G. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03865-5 · Cited by 4
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Rodriguez-Bryant, A., Papageorgiou, M., Horcajada, M.-N., Biver, E., Ferrari, S., & Bonnet, N. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2675093 · Cited by 6
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Koren, O., Collado, M. C., Chassaing, B., Silverman, M. A., & Konnikova, L. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117556 · Cited by 7
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Wei, G., Shi, Z., Wu, X., & Hwang, S. T. (2023) · Journal of Psoriasis and Psoriatic Arthritis · doi:10.1177/24755303231177965 · Cited by 4
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Feng, B., Liu, H., Yao, W., Li, Y., Wu, G., Yang, L.-T., & Yang, P. (2024) · Inflammation Research · doi:10.1007/s00011-023-01841-w · Cited by 4
Epimedium polysaccharides mitigates Porphyromonas gingivalis-exacerbated intestinal inflammation by suppressing the Th17 pathway and modulating the gut microbiota
Li, M., Qu, R., Li, P., Mo, X., Liu, J., Dong, B., Liu, L., & Xu, Z. Z. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.134203 · Cited by 4

Authors: Hang, S., Paik, D., Yao, L., Kim, E., Trinath, J., Lu, J., Ha, S., Nelson, B. N., Kelly, S. P., Wu, L., Zheng, Y., Longman, R. S., Rastinejad, F., Devlin, A. S., Krout, M. R., Fischbach, M. A., Littman, D. R., & Huh, J. R.
Affiliations: Harvard University (US)
Birla Institute of Technology and Science - Hyderabad Campus (IN)
Bucknell University (US)
New York University (US)
Salk Institute for Biological Studies (US)
Weill Cornell Medicine (US)
University of Oxford (GB)
Stanford University (US)
Howard Hughes Medical Institute (US)
Brigham and Women's Hospital (US)
Corresponding author: Fischbach, Michael A.
Littman, Dan R.
Huh, Jun R.
ORCID: Hang, Saiyu
Paik, Donggi
Yao, Lina
Kim, Eunha
Trinath, Jamma
Ha, Soyoung
Wu, Lin
Zheng, Ye
Longman, Randy S.
Rastinejad, Fraydoon
Devlin, A. Sloan
Krout, Michael R.
Fischbach, Michael A.
Littman, Dan R.
Huh, Jun R.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2019-11-27
Volume: 576
Issue: 7785
Pages: 143-148
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-019-1785-z
PMC: PMC6949019
OpenAlex: W2990182987
Cited by: 1,457
References: 59
Citations by year: 2026: 274 · 2025: 287 · 2024: 260 · 2023: 207 · 2022: 174 · 2021: 158 · 2020: 94 · 2019: 3
FWCI: 43.07
Type: journal article
Language: en
Update notices: correction (2020-02-25)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
Wellcome Trust (210664/Z/18/Z)
National Institute of Allergy and Infectious Diseases (R01AI107027, R01AI080885)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK103358, R01DK114252, R01DK110559, P30DK034854)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords: bile acid metabolites, lithocholic acid, Th17 cell differentiation, regulatory T cells, RORγt, Foxp3, mitochondrial reactive oxygen species, gut microbiota, intestinal lamina propria, IL-17A, T cell regulation
MeSH terms: Animals, Cell Differentiation, Lithocholic Acid, Mice, Inbred C57BL, Reactive Oxygen Species, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Th17 Cells

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Bile acid metabolites control TH17 and Treg cell differentiation

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