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العنوان
The balance between regulatory and effector T cells in psoriasis /
المؤلف
Kotb, Iman.
هيئة الاعداد
باحث / إيمان قطب
مشرف / أنتوني أورميرود
مشرف / روبرت بركر
الموضوع
T cells. Psoriasis. Skin Diseases. Skin - Diseases.
تاريخ النشر
2015.
عدد الصفحات
255 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الأمراض الجلدية
تاريخ الإجازة
1/3/2018
مكان الإجازة
جامعة المنصورة - كلية الطب - Dermatology
الفهرس
Only 14 pages are availabe for public view

from 253

from 253

Abstract

Psoriasis is a chronic relapsing T-cell mediated skin disease with marked socio-economic burden. Currently available treatments remain unsatisfactory and are associated with unpredictable remission time, thus the need for new therapeutic strategies is increasingly required. Recent understanding of psoriasis pathogenesis indicates that imbalance between effector (Teff), particularly Th17 cells, and regulatory T cells (Tregs) is a key factor in development of lesions. As Tregs are responsible for immune tolerance, theoretically, the ideal treatment for psoriasis is dependent on skewing this critical balance in favour of Tregs. Identifying gene expression underlying Th17/Tregs pathway is equally important. We compared the response to treatment with therapies currently licensed for use in psoriasis including : calcipotriol/betamethasone combination (DovobetP®P), oral acitretin, narrow band UVB (NB-UVB) and anti TNF-α by using LSRII flow cytometric analysis. The greatest effect on Tregs was found with NB-UVB therapy and to less extent with DovobetP®P, while anti TNF-α has significantly affected Th17 cells with minor effect on Tregs. To further understand the mechanism of Tregs enhancement by NB-UVB, we studied its effect on resident dermal dendritic cells characterised by CD1c and CD141 expression, and known to maintain immune homeostasis. This showed non-significant change in the numbers of these cells. Re-analysis of previously published psoriasis gene expression data using the same stringency threshold and software identified 12 of 92 genes known to be related to the Th17 and Tregs signaling pathways, to be differentially expressed in the lesional skin. Seventy three probe sets representing 57 genes were commonly up-regulated in lesional skin from all datasets. In addition, 26 probe sets representing 20 genes with no previous link to the aetiopathogenesis of psoriasis have been identified. These genes may represent novel therapeutic targets and will need more rigorous experimental testing to be validated.