Rapid activation and hepatic recruitment of innate-like regulatory B cells after invariant NKT cell stimulation in mice

被引:18
作者
Almishri, Wagdi [2 ]
Deans, Julie [1 ,4 ]
Swain, Mark G. [1 ,2 ,3 ]
机构
[1] Snyder Inst, Immunol Res Grp, Calgary, AB, Canada
[2] Snyder Inst, Gastrointestinal Res Grp, Calgary, AB, Canada
[3] Univ Calgary, Div Gastroenterol, Liver Unit, Dept Med, Calgary, AB T2 N 4Z6, Canada
[4] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2 N 4Z6, Canada
基金
加拿大健康研究院;
关键词
alpha-galactosylceramide; Cytokine; CD20; IL-10; Co-stimulatory molecules; CD73; KILLER T-CELLS; LIVER-INJURY; B-1; CELLS; B10; ALPHA; AUTOIMMUNITY; RITUXIMAB; INFLAMMATION; IMMUNITY; ROLES;
D O I
10.1016/j.jhep.2015.06.007
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Invariant 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 alpha-galactosylceramide; alpha GalCer), 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. Methods: Wild-type (male, C57BL/6), B cell deficient, or B cell depleted mice were injected with alpha GalCer or vehicle, hepatic B cell phenotype and liver injury was subsequently determined. Results: iNKT 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 TGF beta, and express cell surface CD73 (ectoenzyme which generates adenosine). B cell deficient mice developed augmented alpha GalCer-induced hepatitis, enhanced neutrophil recruitment and striking alterations in the hepatic cytokine milieu. alpha GalCer-induced hepatitis was unaltered in IL-10(-/-) mice, or after TGFb neutralization, but was significantly worsened in mice treated with a CD73 inhibitor. Conclusions: iNKT cell stimulation recruits innate-like regulatory B cells to the liver which suppress hepatic inflammation through IL-10 and TGF beta 1 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. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:943 / 951
页数:9
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