Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions
Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated with gluten-sensitive enteropathy (CD). In order to investigate the pathogenesis of skin lesions at molecular level, we analysed the gene expression profiles in skin biopsies from 6 CD patients with DH and 6 healthy co...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/198956 |
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| author | M. Dolcino E. Cozzani S. Riva A. Parodi E. Tinazzi C. Lunardi A. Puccetti |
| author_facet | M. Dolcino E. Cozzani S. Riva A. Parodi E. Tinazzi C. Lunardi A. Puccetti |
| author_sort | M. Dolcino |
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| description | Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated with gluten-sensitive enteropathy (CD). In order to investigate the pathogenesis of skin lesions at molecular level, we analysed the gene expression profiles in skin biopsies from 6 CD patients with DH and 6 healthy controls using Affymetrix HG-U133A 2.0 arrays. 486 genes were differentially expressed in DH skin compared to normal skin: 225 were upregulated and 261 were downregulated. Consistently with the autoimmune origin of DH, functional classification of the differentially expressed genes (DEGs) indicates a B- and T-cell immune response (LAG3, TRAF5, DPP4, and NT5E). In addition, gene modulation provides evidence for a local inflammatory response (IL8, PTGFR, FSTL1, IFI16, BDKRD2, and NAMPT) with concomitant leukocyte recruitment (CCL5, ENPP2), endothelial cell activation, and neutrophil extravasation (SELL, SELE). DEGs also indicate overproduction of matrix proteases (MMP9, ADAM9, and ADAM19) and proteolytic enzymes (CTSG, ELA2, CPA3, TPSB2, and CMA1) that may contribute to epidermal splitting and blister formation. Finally, we observed modulation of genes involved in cell growth inhibition (CGREF1, PA2G4, and PPP2R1B), increased apoptosis (FAS, TNFSF10, and BASP1), and reduced adhesion at the dermal epidermal junction (PLEC1, ITGB4, and LAMA5). In conclusion, our results identify genes that are involved in the pathogenesis of DH skin lesions. |
| format | Article |
| id | doaj-art-424df4b97ff447cab9679e527e63abb8 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-424df4b97ff447cab9679e527e63abb82025-02-03T07:25:49ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/198956198956Gene Expression Profiling in Dermatitis Herpetiformis Skin LesionsM. Dolcino0E. Cozzani1S. Riva2A. Parodi3E. Tinazzi4C. Lunardi5A. Puccetti6Instituto Giannina Gaslini, Clinical Immunology Unit, 16148 Genoa, ItalySection of Dermatology, Department of Health Sciences, University of Genoa, 16132 Genoa, ItalySection of Dermatology, Department of Health Sciences, University of Genoa, 16132 Genoa, ItalySection of Dermatology, Department of Health Sciences, University of Genoa, 16132 Genoa, ItalySection of Internal Medicine, Department of Medicine, University of Verona, 37134 Verona, ItalySection of Internal Medicine, Department of Medicine, University of Verona, 37134 Verona, ItalyInstituto Giannina Gaslini, Clinical Immunology Unit, 16148 Genoa, ItalyDermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated with gluten-sensitive enteropathy (CD). In order to investigate the pathogenesis of skin lesions at molecular level, we analysed the gene expression profiles in skin biopsies from 6 CD patients with DH and 6 healthy controls using Affymetrix HG-U133A 2.0 arrays. 486 genes were differentially expressed in DH skin compared to normal skin: 225 were upregulated and 261 were downregulated. Consistently with the autoimmune origin of DH, functional classification of the differentially expressed genes (DEGs) indicates a B- and T-cell immune response (LAG3, TRAF5, DPP4, and NT5E). In addition, gene modulation provides evidence for a local inflammatory response (IL8, PTGFR, FSTL1, IFI16, BDKRD2, and NAMPT) with concomitant leukocyte recruitment (CCL5, ENPP2), endothelial cell activation, and neutrophil extravasation (SELL, SELE). DEGs also indicate overproduction of matrix proteases (MMP9, ADAM9, and ADAM19) and proteolytic enzymes (CTSG, ELA2, CPA3, TPSB2, and CMA1) that may contribute to epidermal splitting and blister formation. Finally, we observed modulation of genes involved in cell growth inhibition (CGREF1, PA2G4, and PPP2R1B), increased apoptosis (FAS, TNFSF10, and BASP1), and reduced adhesion at the dermal epidermal junction (PLEC1, ITGB4, and LAMA5). In conclusion, our results identify genes that are involved in the pathogenesis of DH skin lesions.http://dx.doi.org/10.1155/2012/198956 |
| spellingShingle | M. Dolcino E. Cozzani S. Riva A. Parodi E. Tinazzi C. Lunardi A. Puccetti Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions Clinical and Developmental Immunology |
| title | Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions |
| title_full | Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions |
| title_fullStr | Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions |
| title_full_unstemmed | Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions |
| title_short | Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions |
| title_sort | gene expression profiling in dermatitis herpetiformis skin lesions |
| url | http://dx.doi.org/10.1155/2012/198956 |
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