کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6102829 1211120 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ArticleRapid activation and hepatic recruitment of innate-like regulatory B cells after invariant NKT cell stimulation in mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Research ArticleRapid activation and hepatic recruitment of innate-like regulatory B cells after invariant NKT cell stimulation in mice
چکیده انگلیسی

Background & AimsInvariant natural killer T (iNKT) cells are present within the liver and have been implicated in the development of many liver diseases. Upon activation by glycolipid ligands (including α-galactosylceramide; αGalCer), hepatic iNKT cells produce numerous cytokines and recruit both pro-inflammatory and regulatory immune cells. However, the involvement of B cells in this process is poorly defined.MethodsWild-type (male, C57BL/6), B cell deficient, or B cell depleted mice were injected with αGalCer or vehicle, hepatic B cell phenotype and liver injury was subsequently determined.ResultsiNKT cell activation resulted in liver injury and the rapid activation and hepatic recruitment of B cells (mainly innate-like B1 and MZ-like B cells) from the spleen and peritoneal cavity. B cells recruited to the liver produce IL-10 and TGFβ, and express cell surface CD73 (ectoenzyme which generates adenosine). B cell deficient mice developed augmented αGalCer-induced hepatitis, enhanced neutrophil recruitment and striking alterations in the hepatic cytokine milieu. αGalCer-induced hepatitis was unaltered in IL-10−/− mice, or after TGFβ neutralization, but was significantly worsened in mice treated with a CD73 inhibitor.ConclusionsiNKT cell stimulation recruits innate-like regulatory B cells to the liver which suppress hepatic inflammation through IL-10 and TGFβ1 independent mechanisms, but involve CD73 activity. These findings highlight an important inflammation suppressing role for B cells at early time points during the development of an innate immune response within the liver, and represent a potential therapeutic target for the treatment of liver disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 63, Issue 4, October 2015, Pages 943-951
نویسندگان
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