The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Tight junction defects in patients with atopic dermatitis
Open accessAbstract
Background Atopic dermatitis (AD) is characterized by dry skin and a hyperreactive immune response to allergens, two cardinal features that are caused in part by epidermal barrier defects. Tight junctions (TJ) reside immediately below the stratum corneum and regulate the selective permeability of the paracellular pathway. Objective We evaluated the expression/function of the TJ protein, claudin-1 in epithelium from AD and nonatopic (NA) subjects and screened two American populations for SNPs in CLDN1. Methods Expression profiles of nonlesional epithelium from extrinsic AD, NA and psoriasis subjects were generated using Illumina’s BeadChips. Dysregulated intercellular proteins were validated by tissue staining and qPCR. Bioelectric properties of epithelium were measured in Ussing chambers. Functional relevance of claudin-1 was assessed using a knockdown approach in primary human keratinocytes (PHK). Twenty seven haplotype-tagging SNPs in CLDN1 were screened in two independent AD populations. Results We observed strikingly reduced expression of the TJ proteins claudin-1 and -23 only in AD, which were validated at the mRNA and protein levels. Claudin-1 expression inversely correlated with Th2 biomarkers. We observed a remarkable impairment of the bioelectric barrier function in AD epidermis. In vitro, we confirmed that silencing claudin-1 expression in human keratinocytes diminishes TJ function while enhancing keratinocyte proliferation. Finally, CLDN1 haplotype-tagging single nucleotide polymorphisms revealed associations with AD in two North American populations. Conclusion Taken together, these data suggest that an impaired epidermal TJ is a novel feature of skin barrier dysfunction and immune dysregulation observed in AD, and that CLDN1 may be a new susceptibility gene in this disease.
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
The Structure of Haplotype Blocks in the Human Genome
Gabriel, S. B., Schaffner, S. F., Nguyen, H., Moore, J. M., Roy, J., Blumenstiel, B., Higgins, J., DeFelice, M., Lochner, A., Faggart, M., et al. (2002) · Science · doi:10.1126/science.1069424 · Cited by 5,863
Palmer, C. N. A., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., Goudie, D. R., Sandilands, A., Campbell, L. E., Smith, F. J. D., et al. (2006) · Nature Genetics · doi:10.1038/ng1767 · Cited by 2,978
Claudin-based tight junctions are crucial for the mammalian epidermal barrier
Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y., Noda, T., Kubo, A., & Tsukita, S. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110122 · Cited by 1,512
The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis
Hanifin, J. M., Thurston, M., Omoto, M., Cherill, R., Tofte, S. J., Graeber, M., & Evaluator Group, T. E. (2001) · Experimental Dermatology · doi:10.1034/j.1600-0625.2001.100102.x · Cited by 1,200
Self-citationTight junctions/adherens junctions: basic structure and function
Niessen, C. M. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700865 · Cited by 756
Human zonulin, a potential modulator of intestinal tight junctions
Wang, W., Uzzau, S., Goldblum, S. E., & Fasano, A. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.24.4435 · Cited by 470
Cited by
Weidinger, S., & Novak, N. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00149-x · Cited by 1,908
Self-citationWeidinger, S., Beck, L. A., Bieber, T., Kabashima, K., & Irvine, A. D. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0001-z · Cited by 1,549
Self-citationClaudins and the Modulation of Tight Junction Permeability
Günzel, D., & Yu, A. S. L. (2013) · Physiological Reviews · doi:10.1152/physrev.00019.2012 · Cited by 1,456
Filaggrin Mutations Associated with Skin and Allergic Diseases
Irvine, A. D., McLean, W. H. I., & Leung, D. Y. M. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1011040 · Cited by 1,217
Self-citationBarrier Epithelial Cells and the Control of Type 2 Immunity
Hammad, H., & Lambrecht, B. N. (2015) · Immunity · doi:10.1016/j.immuni.2015.07.007 · Cited by 847
Metadata
- Authors
- De Benedetto, A., Rafaels, N. M., McGirt, L. Y., Ivanov, A. I., Georas, S. N., Cheadle, C., Berger, A. E., Zhang, K., Vidyasagar, S., Yoshida, T., Boguniewicz, M., Hata, T., Schneider, L. C., Hanifin, J. M., Gallo, R. L., Novak, N., Weidinger, S., Beaty, T. H., Leung, D. Y. M., Barnes, K. C., & Beck, L. A.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 127
- Issue
- 3
- Pages
- 773-786.e7
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2063748338
- Cited by
- 747
- References
- 7
- FWCI
- 34.06
- Type
- journal article
- Language
- en
- Open access
- green
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- De Benedetto, A., Rafaels, N. M., McGirt, L. Y., Ivanov, A. I., Georas, S. N., Cheadle, C., Berger, A. E., Zhang, K., Vidyasagar, S., Yoshida, T., Boguniewicz, M., Hata, T., Schneider, L. C., Hanifin, J. M., Gallo, R. L., Novak, N., Weidinger, S., Beaty, T. H., Leung, D. Y. M., . . . Beck, L. A. (2011). Tight junction defects in patients with atopic dermatitis. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2010.10.018
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