دورية أكاديمية
Human gut bacterial metabolism drives Th17 activation and colitis.
| العنوان: | Human gut bacterial metabolism drives Th17 activation and colitis. |
|---|---|
| المؤلفون: | Alexander M; Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Ang QY; Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA 94143, USA., Nayak RR; Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA., Bustion AE; Gladstone Institutes, San Francisco, CA 94158, USA., Sandy M; Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA., Zhang B; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA., Upadhyay V; Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA., Pollard KS; Gladstone Institutes, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94158, USA., Lynch SV; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA., Turnbaugh PJ; Department of Microbiology & Immunology, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: peter.turnbaugh@ucsf.edu. |
| المصدر: | Cell host & microbe [Cell Host Microbe] 2022 Jan 12; Vol. 30 (1), pp. 17-30.e9. Date of Electronic Publication: 2021 Nov 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101302316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1934-6069 (Electronic) Linking ISSN: 19313128 NLM ISO Abbreviation: Cell Host Microbe Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press |
| مواضيع طبية MeSH: | Colitis/*metabolism , Gastrointestinal Microbiome/*physiology , Lymphocyte Activation/*physiology , Th17 Cells/*metabolism, Actinobacteria ; Animals ; Bacteria/metabolism ; Colitis/immunology ; Cytokines ; Dietary Supplements ; Disease Models, Animal ; Female ; Humans ; Inflammatory Bowel Diseases/microbiology ; Interleukin-17/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism |
| مستخلص: | Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms. E. lenta is enriched in inflammatory bowel disease (IBD) patients and worsens colitis in a Rorc-dependent manner in mice. Th17 activation varies across E. lenta strains, which is attributable to the cardiac glycoside reductase 2 (Cgr2) enzyme. Cgr2 is sufficient to induce interleukin (IL)-17a, a major Th17 cytokine. cgr2+ E. lenta deplete putative steroidal glycosides in pure culture; related compounds are negatively associated with human IBD severity. Finally, leveraging the sensitivity of Cgr2 to dietary arginine, we prevented E. lenta-induced intestinal inflammation in mice. Together, these results support a role for human gut bacterial metabolism in driving Th17-dependent autoimmunity. Competing Interests: Declaration of interests P.J.T. is on the scientific advisory board for Kaleido, Pendulum, and SNIPRbiome. K.S.P. is on the scientific advisory board of Phylagen. S.V.L. is a co-founder, board member, and consultant for Siolta Therapeutics Inc. This work was partially supported by a MedImmune research grant. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Cell Host Microbe. 2022 Jan 12;30(1):10-12. doi: 10.1016/j.chom.2021.12.014. (PMID: 35026131) |
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| معلومات مُعتمدة: | T32 AI060537 United States AI NIAID NIH HHS; T32 HL007185 United States HL NHLBI NIH HHS; K08 AR073930 United States AR NIAMS NIH HHS; TL1 TR001871 United States TR NCATS NIH HHS; R01 HL122593 United States HL NHLBI NIH HHS; F32 AI147456 United States AI NIAID NIH HHS; T32 GM007175 United States GM NIGMS NIH HHS; R01 AR074500 United States AR NIAMS NIH HHS; P30 DK063720 United States DK NIDDK NIH HHS; R21 CA227232 United States CA NCI NIH HHS; R01 DK114034 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: T helper 17 cells; autoimmune disease; dietary supplementation; human gut microbiome; inflammatory bowel disease; microbial metabolism |
| المشرفين على المادة: | 0 (Cytokines) 0 (IL17A protein, human) 0 (Interleukin-17) 0 (Nuclear Receptor Subfamily 1, Group F, Member 3) 0 (RORC protein, human) |
| SCR Organism: | Eggerthella lenta |
| تواريخ الأحداث: | Date Created: 20211125 Date Completed: 20220218 Latest Revision: 20240923 |
| رمز التحديث: | 20240923 |
| مُعرف محوري في PubMed: | PMC8785648 |
| DOI: | 10.1016/j.chom.2021.11.001 |
| PMID: | 34822777 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1934-6069 |
|---|---|
| DOI: | 10.1016/j.chom.2021.11.001 |