Regulation of tissue immune responses by local glucocorticoids at epithelial barriers and their impact on interorgan crosstalk
Open accessAbstract
The anti-inflammatory role of extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers is of increasing interest with regard to the search for alternatives to synthetic corticosteroids in the therapy of inflammatory disorders. Despite being very effective in many situations the use of synthetic corticosteroids is often controversial, as exemplified in the treatment of influenza patients and only recently in the current COVID-19 pandemic. Exploring the regulatory capacity of locally produced GCs in balancing immune responses in barrier tissues and in pathogenic disorders that lead to symptoms in multiple organs, could provide new perspectives for drug development. Intestine, skin and lung represent the first contact zones between potentially harmful pathogens or substances and the body, and are therefore important sites of immunoregulatory mechanisms. Here, we review the role of locally produced GCs in the regulation of type 2 immune responses, like asthma, atopic dermatitis and ulcerative colitis, as well as type 1 and type 3 infectious, inflammatory and autoimmune diseases, like influenza infection, psoriasis and Crohn's disease. In particular, we focus on the role of locally produced GCs in the interorgan communication, referred to as gut-skin axis, gut-lung axis or lung-skin axis, all of which are interconnected in the pathogenic crosstalk atopic march.
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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 [525]
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- Authors
- Merk, V. M., Phan, T. S., & Brunner, T.
- Affiliations
- University of Konstanz (DE)
- Corresponding author
- Brunner, Thomas
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2021-05-03
- Volume
- 12
- Pages
- 672808-672808
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC8127840
- OpenAlex
- W3159275666
- Cited by
- 27
- References
- 99
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 9 · 2022: 7 · 2021: 2 · 2012: 1
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KOPS (University of Konstanz) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- epithelial barrier function, organ crosstalk, Th2 immune response, type 1 immune response, type 3 immunity, asthma, atopic dermatitis, ulcerative colitis, influenza, psoriasis, Crohn's disease, gut-skin axis, gut-lung axis, atopic march, anti-inflammatory drug development, synthetic corticosteroids
- MeSH terms
- Anti-Inflammatory Agents, Autoimmune Diseases, Dermatitis, Atopic, Epithelium, Glucocorticoids, Humans, Inflammation, Intestinal Mucosa, Lung, Skin
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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