ArticleProceedings of the National Academy of Sciences of the United States of America2021
Interleukins 4 and 13 drive lipid abnormalities in skin cells through regulation of sex steroid hormone synthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Pooled it
- Article
- Decoding Sebaceous Gland Biology Through Experimental Models: Progress, Limitations, and Future Directions.Cells · 2026Review
- Salivary OMICS factors associated with atopic dermatitis in early infancy.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- Atopic Dermatitis Beyond Cutaneous Inflammation: The Interplay Between Progesterone, Testosterone, Gut Microbiota, and Immune Dysregulation.Microorganisms · 2026Review
- Skin androgens regulate Staphylococcus aureus pathogenicity via quorum sensing.Nature microbiology · 2026Article
- The potential of targeted IL-4 therapy for the comorbidity of atopic dermatitis and attention-deficit/hyperactivity disorder in children via the skin-brain axis.Frontiers in allergy · 2026Article
- Atopic dermatitis: diagnosis, molecular pathogenesis, and therapeutics.Molecular biomedicine · 2025Review
- Is There a Place for Biologics in Acne?American journal of clinical dermatology · 2025Review
- Cutaneous Hormone Sampling and Analysis for Dermatologic Research.The Journal of investigative dermatology · 2025Review
- The Sebaceous Gland: A Key Player in the Balance Between Homeostasis and Inflammatory Skin Diseases.Cells · 2025Review
- Serum metabolites and risk of aortic dissection: a two-sample Mendelian randomization study.Indian journal of thoracic and cardiovascular surgery · 2025Article
- Insights into early acne pathogenesis: Exploring intercellular dynamics and key dysregulated genes.Cell signaling · 2025Article
- Targeting the IL-4/IL-4R Axis in Th2 Inflammatory Diseases: A Review of Clinical Efficacy and Safety.Journal of inflammation research · 2025Review
- Characterization of Inflammatory Mediators and Metabolome in Interstitial Fluid Collected with Dermal Open Flow Microperfusion before and at the End of Dupilumab Treatment in Atopic Dermatitis.Journal of proteome research · 2024Article
- Thymic stromal lymphopoietin induces IL-4/IL-13 from T cells to promote sebum secretion and adipose loss.The Journal of allergy and clinical immunology · 2024Article
- Article
- Spatial transcriptomics reveals altered lipid metabolism and inflammation-related gene expression of sebaceous glands in psoriasis and atopic dermatitis.Frontiers in immunology · 2024Article
- Association Between Atopic Dermatitis and Aging: Clinical Observations and Underlying Mechanisms.Journal of inflammation research · 2024Review
- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin dryness, inflammation, and itch. A major hallmark of AD is an elevation of the immune cytokines IL-4 and IL-13. These cytokines lead to skin barrier disruption and lipid abnormalities in AD, yet the underlying mechanisms are unclear. Sebaceous glands are specialized sebum-producing epithelial cells that promote skin barrier function by releasing lipids and antimicrobial proteins to the skin surface. Here, we show that in AD, IL-4 and IL-13 stimulate the expression of 3β-hydroxysteroid dehydrogenase 1 (HSD3B1), a key rate-limiting enzyme in sex steroid hormone synthesis, predominantly expressed by sebaceous glands in human skin. HSD3B1 enhances androgen production in sebocytes, and IL-4 and IL-13 drive lipid abnormalities in human sebocytes and keratinocytes through HSD3B1. Consistent with our findings in cells, HSD3B1 expression is elevated in the skin of AD patients and can be restored by treatment with the IL-4Rα monoclonal antibody, Dupilumab. Androgens are also elevated in a mouse model of AD, though the mechanism in mice remains unclear. Our findings illuminate a connection between type 2 immunity and sex steroid hormone synthesis in the skin and suggest that abnormalities in sex steroid hormone synthesis may underlie the disrupted skin barrier in AD. Furthermore, targeting sex steroid hormone synthesis pathways may be a therapeutic avenue to restoring normal skin barrier function in AD patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.