کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3299147 | 1209923 | 2008 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
PD-1 Ligand Expression by Human Colonic Myofibroblasts/Fibroblasts Regulates CD4+ T-Cell Activity
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کلمات کلیدی
APCLPMNCUTMBCMFmAbα-SMAnatural killer - (سلول های) کشنده طبیعیSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAMonoclonal antibody - آنتی بادی مونوکلونالantigen-presenting cell - آنتیژن ارائه سلولα-smooth muscle actin - اکتین عضله آلفا صافimmunoglobulin - ایمونوگلوبولینinterleukin - اینترلوکینEnzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاlamina propria mononuclear cell - سلول تک هسته ای لامین پروپریاDendritic cell - سلول دندریتیکMHC - مجموعه سازگاری بافتی اصلیmajor histocompatibility complex - مجموعه سازگاری بافتی اصلی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Background & Aims: A prominent role for inhibitory molecules PD-L1 and PD-L2 in peripheral tolerance has been proposed. However, the phenotype and function of PD-L-expressing cells in human gut remains unclear. Recent studies suggest that colonic myofibroblasts (CMFs) and fibroblasts are important in the switch from acute inflammation to adaptive immunity. In the normal human colon, CMFs represent a distinct population of major histocompatibility complex class II+ cells involved in the regulation of mucosal CD4+ T-cell responses. Methods: PD-L1 and PD-L2 expression on human CMFs was determined using Western blot, fluorescence-activated cell sorter analysis and confocal microscopy. Lymphoproliferation assays and cytokine enzyme-linked immunosorbent assays were used to evaluate the role of B7 costimulators expressed by CMFs with regard to the regulation of preactivated T-helper cell responses. Results: We demonstrate here the expression of PD-L1/2 molecules by normal human CMF and fibroblasts in situ and in culture. Both molecules support suppressive functions of CMFs in the regulation of activated CD4+ T-helper cell proliferative responses; blocking this interaction reverses the suppressive effect of CMFs on T-cell proliferation and leads to increased production of the major T-cell growth factor, interleukin (IL)-2. PD-L1/2-mediated CMF suppressive functions are mainly due to the inhibition of IL-2 production, because supplementation of the coculture media with exogenous IL-2 led to partial recovery of activated T-cell proliferation. Conclusions: Our data suggest that stromal myofibroblasts and fibroblasts may limit T-helper cell proliferative activity in the gut and, thus, might play a prominent role in mucosal intestinal tolerance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 135, Issue 4, October 2008, Pages 1228-1237.e2
Journal: Gastroenterology - Volume 135, Issue 4, October 2008, Pages 1228-1237.e2
نویسندگان
Irina V. Pinchuk, Jamal I. Saada, Ellen J. Beswick, Gushyalatha Boya, Sumin M. Qiu, Randy C. Mifflin, Gottumukkala S. Raju, Victor E. Reyes, Don W. Powell,