Cited by 45Gut microbiota and healthGenomics and Chromatin DynamicsT-cell and B-cell Immunology

Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes

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Semenkovich, Nicholas P., Planer, Joseph D., Ahern, Philip P., Griffin, Nicholas W., Lin, Charles Y., Gordon, Jeffrey I.·2016·Proceedings of the National Academy of Sciences

Abstract

Significance: Comparing germ-free mice with those colonized at birth or later provides a way to determine how gut microbial community exposure affects the chromatin landscape of cells along the gut or at remote sites, ascertain how alterations in chromatin accessibility are correlated with functional features of different lineages, and determine whether there is a critical window of exposure when microbial signals must be received to alter the landscape durably. Genome-wide analysis of chromatin accessibility in intraepithelial lymphocytes and circulating T cells purified from gnotobiotic mice revealed enhancers and flanking genes involved in signaling and metabolic pathways that are sensitive to colonization status. Colonization does not fundamentally alter lineage-specific cis -regulatory landscapes but induces quantitative changes in the accessibility of preestablished enhancer elements.

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  • Chromatin accessibility of intestinal intraepithelial lymphocytes is quantitatively changed in germ-free mice colonized by conventional microbiota, resulting in determination of functional features of host immune cell lineages.

    “The chromatin accessibility of intestinal intraepithelial lymphocytes was quantitatively changed in germ-free mice colonized by conventional microbiota, resulting in determination of functional features ofhost immune cell lineages201.”

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Research works printed but not linked: 2

  1. Smith PM, et al. (2013) The microbial metabolites, short-chain fatty acids, regulate colonic treg cell homeostasis. Science 341(6145):569-573.
  2. Joller N, et al. (2014) Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity 40(4):569-581.

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Authors
Semenkovich, N. P., Planer, J. D., Ahern, P. P., Griffin, N. W., Lin, C. Y., & Gordon, J. I.
Affiliations
  • Washington University in St. Louis (US)
  • Baylor College of Medicine (US)
Corresponding author
Gordon, Jeffrey I.
Venue
Proceedings of the National Academy of Sciences
Published
2016-12
Volume
113
Issue
51
Pages
14805-14810
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2559723230
Cited by
45
References
66
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 1
FWCI
2.60
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK030292, DK070977, DK078669)
  • HHS | National Institutes of Health (T32HG000045, GM007200)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
gut microbiota, chromatin accessibility, enhancers, intraepithelial lymphocytes, germ-free mice, microbial colonization, gnotobiotic mice, T cells, cis-regulatory elements
MeSH terms
Gastrointestinal Microbiome, Intraepithelial Lymphocytes, Animals, Chromatin, Enhancer Elements, Genetic, Germ-Free Life, Intestinal Mucosa, Intestines, Male, Mice, Inbred C57BL, Signal Transduction, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Lineage, Mice

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