دورية أكاديمية
Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity.
| العنوان: | Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity. |
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| المؤلفون: | Chun E; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Lavoie S; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Fonseca-Pereira D; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Bae S; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Michaud M; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Hoveyda HR; Euroscreen SA, 6041 Gosselies, Belgium., Fraser GL; EPICS SA, 6041 Gosselies, Belgium., Gallini Comeau CA; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Glickman JN; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Fuller MH; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Layden BT; Division of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, IL 60612, USA; Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA., Garrett WS; Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: wgarrett@hsph.harvard.edu. |
| المصدر: | Immunity [Immunity] 2019 Nov 19; Vol. 51 (5), pp. 871-884.e6. Date of Electronic Publication: 2019 Oct 15. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994- |
| مواضيع طبية MeSH: | Immunity, Innate* , Immunity, Mucosal*, Intestinal Mucosa/*immunology , Intestinal Mucosa/*metabolism , Lymphocytes/*immunology , Lymphocytes/*metabolism , Receptors, Cell Surface/*metabolism, Animals ; Biomarkers ; Cytokines/metabolism ; Disease Susceptibility ; Gastrointestinal Microbiome/immunology ; Gene Expression ; Humans ; Immunomodulation ; Intestinal Mucosa/pathology ; Lymphocyte Activation/immunology ; Mice ; Mice, Knockout ; Proto-Oncogene Proteins c-akt ; Receptors, Cell Surface/agonists ; STAT3 Transcription Factor/metabolism |
| مستخلص: | Group 3 innate lymphoid cells (ILC3s) sense environmental signals that are critical for gut homeostasis and host defense. However, the metabolite-sensing G-protein-coupled receptors that regulate colonic ILC3s remain poorly understood. We found that colonic ILC3s expressed Ffar2, a microbial metabolite-sensing receptor, and that Ffar2 agonism promoted ILC3 expansion and function. Deficiency of Ffar2 in ILC3s decreased their in situ proliferation and ILC3-derived interleukin-22 (IL-22) production. This led to impaired gut epithelial function characterized by altered mucus-associated proteins and antimicrobial peptides and increased susceptibility to colonic injury and bacterial infection. Ffar2 increased IL-22 + CCR6 + ILC3s and influenced ILC3 abundance in colonic lymphoid tissues. Ffar2 agonism differentially activated AKT or ERK signaling and increased ILC3-derived IL-22 via an AKT and STAT3 axis. Our findings suggest that Ffar2 regulates colonic ILC3 proliferation and function, and they identify an ILC3-receptor signaling pathway modulating gut homeostasis and pathogen defense. (Copyright © 2019 Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Immunity. 2019 Nov 19;51(5):786-788. (PMID: 31747578) |
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| معلومات مُعتمدة: | I01 BX003382 United States BX BLRD VA; R01 CA154426 United States CA NCI NIH HHS; R01 DK104927 United States DK NIDDK NIH HHS; R24 DK110499 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: AKT; CCR6; Ffar2(GPR43); IL-22; ILC3; SCFA; STAT3; colon; gut barrier integrity; innate lymphoid cell; metabolite-sensing GPCR |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Cytokines) 0 (FFA2R protein, human) 0 (Receptors, Cell Surface) 0 (STAT3 Transcription Factor) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
| تواريخ الأحداث: | Date Created: 20191020 Date Completed: 20200122 Latest Revision: 20211008 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6901086 |
| DOI: | 10.1016/j.immuni.2019.09.014 |
| PMID: | 31628054 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4180 |
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| DOI: | 10.1016/j.immuni.2019.09.014 |