کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5649460 | 1407125 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Targeted Resequencing and Functional Testing Identifies Low-Frequency Missense Variants in the Gene Encoding GARP as Significant Contributors to Atopic Dermatitis Risk
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کلمات کلیدی
PBSLAPTregSNVGARPLRRC32TGF-βtransforming growth factor-beta - تبدیل فاکتور رشد بتاAtopic dermatitis - درماتیت آتوپیکRegulatory T cell - سلول T تنظیم کنندهPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریwild type - نوع وحشیlatency associated protein - پروتئین مرتبط با زمان تأخیرsingle nucleotide variant - یک نوع نوکلئوتید تک
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Gene-mapping studies have consistently identified a susceptibility locus for atopic dermatitis and other inflammatory diseases on chromosome band 11q13.5, with the strongest association observed for a common variant located in an intergenic region between the two annotated genes C11orf30 and LRRC32. Using a targeted resequencing approach we identified low-frequency and rare missense mutations within the LRRC32 gene encoding the protein GARP, a receptor on activated regulatory T cells that binds latent transforming growth factor-β. Subsequent association testing in more than 2,000 atopic dermatitis patients and 2,000 control subjects showed a significant excess of these LRRC32 variants in individuals with atopic dermatitis. Structural protein modeling and bioinformatic analysis predicted a disruption of protein transport upon these variants, and overexpression assays in CD4+CD25- T cells showed a significant reduction in surface expression of the mutated protein. Consistently, flow cytometric (FACS) analyses of different T-cell subtypes obtained from atopic dermatitis patients showed a significantly reduced surface expression of GARP and a reduced conversion of CD4+CD25- T cells into regulatory T cells, along with lower expression of latency-associated protein upon stimulation in carriers of the LRRC32 A407T variant. These results link inherited disturbances of transforming growth factor-β signaling with atopic dermatitis risk.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 136, Issue 12, December 2016, Pages 2380-2386
Journal: Journal of Investigative Dermatology - Volume 136, Issue 12, December 2016, Pages 2380-2386
نویسندگان
Judith Manz, Elke RodrÃguez, Abdou ElSharawy, Eva-Maria Oesau, Britt-Sabina Petersen, Hansjörg Baurecht, Gabriele Mayr, Susanne Weber, Jürgen Harder, Eva Reischl, Agatha Schwarz, Natalija Novak, Andre Franke, Stephan Weidinger,