title: Rapid activation and hepatic recruitment of innate-like regulatory B cells after invariant NKT cell stimulation in mice.
abstract: OBJECTIVE
  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 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.
  
  
  METHODS
  Wild-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.
  
  
  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 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.
  
  
  CONCLUSIONS
  iNKT 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.
authors.affiliation: Gastrointestinal Research Groups, Snyder Institute, Canada.
authors.forename: Wagdi
authors.initials: W
authors.lastname: Almishri
authors.affiliation: Immunology and Snyder Institute, Canada; Department of Biochemistry and Molecular Biology, University of Calgary, Alberta, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Deans
authors.affiliation: Immunology and Snyder Institute, Canada; Gastrointestinal Research Groups, Snyder Institute, Canada; Liver Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Alberta, Canada. Electronic address: swain@ucalgary.ca.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Swain
mesh_terms: D015720:5'-Nucleotidase / Q000276:immunology / Q000378:metabolism; D000818:Animals; D060151:B-Lymphocytes, Regulatory; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006505:Hepatitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D010641:Phenotype
chemical_list: D016207:Cytokines; D015720:5'-Nucleotidase
keywords: CD20; CD73; Co-stimulatory molecules; Cytokine; IL-10; α-galactosylceramide