GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology.

Autor:	Earley ZM; Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA., Lisicka W; Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA., Sifakis JJ; Department of Chemistry, University of Chicago, Chicago, IL, USA., Aguirre-Gamboa R; Department of Medicine, University of Chicago, Chicago, IL, USA., Kowalczyk A; Department of Medicine, University of Chicago, Chicago, IL, USA., Barlow JT; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Shaw DG; Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA., Discepolo V; Department of Medical Translational Sciences and European Laboratory for the Investigation of Food Induced Diseases, University of Federico II, Naples, Italy., Tan IL; Department of Gastroenterology and Hepatology, University of Groningen and University of Medical Center Groningen, Groningen, the Netherlands., Gona S; Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA., Ernest JD; Department of Medicine, University of Chicago, Chicago, IL, USA., Matzinger P; Ghost Lab, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Barreiro LB; Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA., Morgun A; College of Pharmacy, Oregon State University, Corvallis, OR, USA., Bendelac A; Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Pathology, University of Chicago, Chicago, IL, USA., Ismagilov RF; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA., Shulzhenko N; Department of Biomedical Sciences, Oregon State University, Corvallis, OR, USA., Riesenfeld SJ; Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA. Electronic address: sriesenfeld@uchicago.edu., Jabri B; Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Department of Pathology, University of Chicago, Chicago, IL, USA; Department of Pediatrics, University of Chicago, Chicago, IL, USA. Electronic address: bjabri@bsd.uchicago.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2023 Jan 10; Vol. 56 (1), pp. 43-57.e10.
DOI:	10.1016/j.immuni.2022.12.009
Abstrakt:	There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA. Furthermore, in mice without jejunal GATA4 expression, the commensal segmented filamentous bacteria promoted pathogenic inflammatory immune responses that disrupted barrier function and increased mortality upon Citrobacter rodentium infection. In celiac disease patients, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. Taken together, these results reveal broad impacts of GATA4-regulated intestinal regionalization on bacterial colonization and tissue immunity, highlighting an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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