Cited by 24Estrogen and related hormone effectsT-cell and B-cell ImmunologyAdrenal Hormones and Disorders

Local synthesis of immunosuppressive glucocorticoids in the intestinal epithelium regulates anti-viral immune responses

Huang, Juan, Jia, Renyong, Brunner, Thomas·2018·Cellular Immunology

Abstract

The nuclear receptor Small Heterodimer Partner (SHP) is a transcriptional target and inhibitor of Liver Receptor Homolog 1 (LRH-1), the transcriptional regulator of intestinal glucocorticoid (GC) synthesis. The role of SHP in the regulation of intestinal GC synthesis and its impact on T cell-mediated anti-viral immune responses in the intestinal mucosa are currently not understood. Lymphocytic choriomeningitis virus (LCMV) infection promoted intestinal GC synthesis, which was enhanced in SHP-deficient mice. Intestinal GC suppressed the expansion and altered the activation of virus-specific T cells. In contrast, deletion of LRH-1 reduced intestinal GC synthesis and accelerated the expansion of cytotoxic T cells post LCMV infection. These findings show that virus-induced intestinal GC synthesis is controlled by LRH-1 and SHP, and that local steroidogenesis contributes to the maintenance of intestinal immune homeostasis. Thus, LRH-1-regulated intestinal GC synthesis could represent an interesting therapeutic target in the treatment of inflammatory disorders.

Integrity signals

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Crossref · 10.1016/j.cellimm.2018.08.009

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  • Extra-adrenal glucocorticoid production occurs in the gut and other tissues, and these glucocorticoids regulate local homeostasis, cell development, and immune activation.

    “Extra-adrenal glucocorticoid production is known to occur in the gut and other tissues, and these glucocorticoids play a highly specific role in regulating local homeostasis, cell development, and immune activation (522–526).”

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Authors
Huang, J., Jia, R., & Brunner, T.
Affiliations
  • University of Konstanz (DE)
  • Sichuan Agricultural University (CN)
Corresponding author
Brunner, Thomas
Venue
Cellular Immunology
Publisher
Elsevier BV
Published
2018-12
Volume
334
Pages
1-10
ISSN
0008-8749 (ISSN-L)
OpenAlex
W2887382103
Cited by
24
References
46
Citations by year
2026: 2 · 2025: 3 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 7
FWCI
1.99
Type
journal article
Language
en
Open access
closed
Locations
  • Cellular Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
German Science Foundation (BR 3369/4-1, INST 38/500-1, INST 38/498-1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
small heterodimer partner, LRH-1, lymphocytic choriomeningitis virus, antiviral response, virus-specific T cells, cytotoxic T lymphocytes, intestinal immune homeostasis, intestinal epithelium, nuclear receptors
MeSH terms
Animals, Female, Glucocorticoids, Homeostasis, Immunosuppressive Agents, Inflammation, Intestinal Mucosa, Intestines, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Male, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Mice

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