The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Filaggrin in atopic dermatitis
Abstract
The recent identification of loss-of-function mutations in the structural protein filaggrin as a widely replicated major risk factor for eczema sheds new light on disease mechanisms in eczema, a disease that had heretofore largely been considered to have a primarily immunologic etiopathogenesis. The filaggrin gene (FLG) mutation findings are consistent with a recently proposed unifying hypothesis that offers a mechanistic understanding of eczema pathogenesis synthesizing a heritable epithelial barrier defect and resultant diminished epidermal defense mechanisms to allergens and microbes, followed by polarized T(H)2 lymphocyte responses with resultant chronic inflammation, including autoimmune mechanisms. Although compelling evidence from genetic studies on FLG implicates perturbed barrier function as a key player in the pathogenesis of eczema in many patients, much is still unknown about the sequence of biologic, physicochemical, and aberrant regulatory events that constitute the transition from an inherited barrier defect to clinical manifestations of inflammatory eczematous lesions and susceptibility to related atopic disorders. The exact contribution of FLG to the wider atopic story, factors modifying FLG expression, and the role of other barrier proteins remain to be delineated. In this review we highlight recent advances in our understanding of the FLG genetics in the cause of eczema and related complex diseases.
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“Furthermore, the incidence and the prevalence of AD in Asian countries, such as China and Korea, where there are high-PM2.5 areas, are similar to those of European ancestry despite FLG mutations being more uncommon in Chinese and Korean ancestry (20, 67, 73, 74).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [74]
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Self-citationThe cornified envelope: a model of cell death in the skin
Candi, E., Schmidt, R., & Melino, G. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1619 · Cited by 1,776
Cytokine modulation of atopic dermatitis filaggrin skin expression
Howell, M. D., Kim, B. E., Gao, P., Grant, A. V., Boguniewicz, M., DeBenedetto, A., Schneider, L., Beck, L. A., Barnes, K. C., & Leung, D. Y. M. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.04.031 · Cited by 1,084
Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris
Smith, F. J. D., Irvine, A. D., Terron-Kwiatkowski, A., Sandilands, A., Campbell, L., Zhao, Y., Liao, H., Evans, A. T., Goudie, D. R., Lewis‐Jones, S., et al. (2006) · Nature Genetics · doi:10.1038/ng1743 · Cited by 1,026
Self-citationMoisturization and skin barrier function
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Self-citationWeidinger, S., Illig, T., Baurecht, H., Irvine, A. D., Rodríguez, E., Diaz-Lacava, A. N., Klopp, N., Wagenpfeil, S., Zhao, Y., Liao, H., et al. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.05.004 · Cited by 619
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Antimicrobial peptides and the skin immune defense system
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Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms
Elias, P. M., Hatano, Y., & Williams, M. L. K. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2008.01.022 · Cited by 466
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Atopic dermatitis: a disease of altered skin barrier and immune dysregulation
Boguniewicz, M., & Leung, D. Y. M. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01027.x · Cited by 1,100
Epidermal Barrier Dysfunction in Atopic Dermatitis
Cork, M. J., Danby, S. G., Vasilopoulos, Y., Hadgraft, J., Lane, M. E., Moustafa, M., Guy, R. H., MacGowan, A., Ahnini, R. T., & Ward, S. J. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.133 · Cited by 800
Atopic dermatitis endotypes and implications for targeted therapeutics
Czarnowicki, T., He, H., Krueger, J. G., & Guttman‐Yassky, E. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.10.032 · Cited by 659
Structure and function of the human skin microbiome
Schommer, N. N., & Gallo, R. L. (2013) · Trends in Microbiology · doi:10.1016/j.tim.2013.10.001 · Cited by 561
Staphylococcus aureus and Atopic Dermatitis: A Complex and Evolving Relationship
Geoghegan, J. A., Irvine, A. D., & Foster, T. J. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2017.11.008 · Cited by 533
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Metadata
- Authors
- O'Regan, G. M., Sandilands, A., McLean, W. H. I., & Irvine, A. D.
- Affiliations
- University of Dundee (GB)
- Trinity College Dublin (IE)
- Corresponding author
- Irvine, Alan D.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 122
- Issue
- 4
- Pages
- 689-693
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W4296927509
- Cited by
- 350
- References
- 25
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 13 · 2023: 14 · 2022: 20 · 2021: 20 · 2020: 29 · 2019: 22 · 2018: 9 · 2017: 15 · 2016: 14 · 2015: 11 · 2014: 17 · 2013: 23 · 2012: 25
- FWCI
- 37.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- filaggrin, FLG gene, atopic dermatitis, loss-of-function mutations, epithelial barrier function, chronic inflammation, autoimmune mechanisms, atopic diseases, genetic susceptibility
- MeSH terms
- Filaggrin Proteins, Animals, Chronic Disease, Dermatitis, Atopic, Eczema, Flagellin, Humans, Inflammation, Mutation, Autoimmunity, Th2 Cells
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