کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6119275 | 1592298 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Distinct from its canonical effects, deletion of IL-12p40 induces cholangitis and fibrosis in interleukin-2Rαâ/â mice
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کلمات کلیدی
IFN-γTh1MLNsMNCsEffector memory cellsPBCT helper 1IL-12p40ALTCCL2HSCserum alanine aminotransferase - آلانین آمینوترانسفراز سرمinterferon γ - اینترفرون γANOVA - تحلیل واریانس Analysis of varianceone-way analysis of variance - تحلیل واریانس یک راههtumor necrosis factor alpha - تومور نکروز عامل آلفاHepatic stellate cell - سلول ستاره ای کبدیMononuclear cells - سلولهای تک هسته ایPrimary biliary cirrhosis - سیروز صفراوی اولیهTNF-α - فاکتور نکروز توموری آلفاFibrosis - فیبروز یا فساد الیافGenome-wide association studies - مطالعات مرتبط با ژنومGWAS - مطالعهٔ همخوانی سراسر ژنومchemokine (C–C motif) ligand 2 - کیموکین (C-C motif) لیگاند 2mesenteric lymph nodes - گره های لنفاوی مزانتریک
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Distinct from its canonical effects, deletion of IL-12p40 induces cholangitis and fibrosis in interleukin-2Rαâ/â mice Distinct from its canonical effects, deletion of IL-12p40 induces cholangitis and fibrosis in interleukin-2Rαâ/â mice](/preview/png/6119275.png)
چکیده انگلیسی
The IL-12 family modulates T cell mediated autoimmune diseases and GWAS in PBC have suggested a critical role of IL-12 and its subunits in modulating portal inflammation. We have taken advantage of an aggressive model of portal inflammation and colitis in IL-2Rαâ/â mice to study the specific role of IL-12 and, in particular, the immunobiology of p40â/âIL-2Rαâ/â mice. Colonies of IL-2Rα+/â, IL-2Rαâ/â and p40â/âIL-2Rαâ/â mice were studied for the natural history of immunopathology in liver and colon using histology and immunohistochemistry. Further, to focus on mechanisms, liver, spleen and mesenteric lymph node flow cytometry was employed to identify specific phenotypes; cytokine analysis on inflammatory cell populations was compared between groups. Finally, Real-Time PCR was used to focus on the genes involved in hepatic fibrosis. Surprisingly, p40â/âIL-2Rαâ/â mice manifest more severe portal inflammation and bile duct damage, including signs of portal hypertension and liver fibrosis, but a significant reduction in colitis. Indeed, p40â/âIL-2Rαâ/â mice reveal a profound hepatic CD8+ T cell infiltrate, whose major component are effector memory cells as well as enhanced hepatic Th1 but reduced Th17 responses. These observations were confirmed by Real-Time PCR analysis of fibrosis-related genes in the liver. Distinct from its canonical effects, IL-12p40 plays a critical role in autoimmune cholangitis, including hepatic fibrosis. These data take on striking significance for any proposed human trials that modulate the IL-12p40 pathway in human PBC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Autoimmunity - Volume 51, June 2014, Pages 99-108
Journal: Journal of Autoimmunity - Volume 51, June 2014, Pages 99-108
نویسندگان
Yuan Yao, Wei Yang, Yan-Qing Yang, Hong-Di Ma, Fang-Ting Lu, Liang Li, Yan-Yan Tao, Koichi Tsuneyama, Weici Zhang, Scott Friedman, M. Eric Gershwin, Zhe-Xiong Lian,