Local synthesis of immunosuppressive glucocorticoids in the intestinal epithelium regulates anti-viral immune responses
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.
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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).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [524]
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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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