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Natural killer T cells mediate inflammation in the bile ducts.

ABSTRACT: Cholangiocytes function as antigen-presenting cells with CD1d-dependent activation of natural killer T (NKT) cells in vitro. NKT cells may act both pro- and anti-inflammatory in liver immunopathology. We explored this immune pathway and the antigen-presenting potential of NKT cells in the bile ducts by challenging wild-type and Cd1d-/- mice with intrabiliary injection of the NKT cell activating agent oxazolone. Pharmacological blocking of CD1d-mediated activation was performed with a monoclonal antibody. Intrabiliary oxazolone injection in wild-type mice caused acute cholangitis with significant weight loss, elevated serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin, increased histologic grade of cholangitis and number of T cells, macrophages, neutrophils and myofibroblasts per portal tract after 7 days. NKT cells were activated after intrabiliary injection of oxazolone with upregulation of activation markers. Cd1d-/- and wild-type mice pretreated with antibody blocking of CD1d were protected from disease. These findings implicate that cells in the bile ducts function as antigen-presenting cells in vivo and activate NKT cells in a CD1d-restricted manner. The elucidation of this biliary immune pathway opens up for potentially new therapeutic approaches for cholangiopathies.

SUBMITTER: Berntsen NL

PROVIDER: S-EPMC6402771 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Natural killer T cells mediate inflammation in the bile ducts.

Berntsen N L NL Fosby B B Tan C C Reims H M HM Ogaard J J Jiang X X Schrumpf E E Valestrand L L Karlsen T H TH Line P-D PD Blumberg R S RS Melum E E

Mucosal immunology 20180816 6

Cholangiocytes function as antigen-presenting cells with CD1d-dependent activation of natural killer T (NKT) cells in vitro. NKT cells may act both pro- and anti-inflammatory in liver immunopathology. We explored this immune pathway and the antigen-presenting potential of NKT cells in the bile ducts by challenging wild-type and Cd1d<sup>-/-</sup> mice with intrabiliary injection of the NKT cell activating agent oxazolone. Pharmacological blocking of CD1d-mediated activation was performed with a ...[more]

PMID: 30115993

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Project description:Infiltrating immune cells play a central role in degenerative joint disease associated with osteoarthritis (OA) and particle-mediated periprosthetic osteolysis. The goal of this study was to characterize a newly identified population of synovial tissue-infiltrating natural killer (NK) cells obtained from patients with OA or patients with periprosthetic joint inflammation.Synovial and interfacial tissue samples were collected from patients with OA who were undergoing primary or revision total joint replacement (TJR) surgery. The histologic features of OA synovium obtained from patients undergoing primary surgery and interfacial tissue obtained from patients undergoing revision surgery were determined by immunohistochemistry and immunofluorescence. Synovial tissue-infiltrating NK cells were evaluated for the expression of surface receptors, using flow cytometry. Chemoattractant and cytokine protein and RNA levels in synovial and interfacial tissue and fluid were assessed by Luminex assay and real-time quantitative polymerase chain reaction. Cytokine production and degranulation by stimulated synovial tissue versus normal blood NK cells were evaluated by intracellular cytokine staining.NK cells comprised nearly 30% of the CD45+ mononuclear cell infiltrate in synovial tissue obtained from patients undergoing primary TJR and from patients undergoing revision TJR. NK cells from both groups expressed CXCR3, CCR5, L-selectin, ?4 integrins, and cutaneous lymphocyte antigen. Synovial fluid from patients undergoing revision surgery contained elevated concentrations of the NK cell attractants CCL4, CCL5, CXCL9, and CXCL10; all levels in synovial fluid obtained from patients undergoing revision surgery were higher than those in synovial fluid from patients undergoing primary surgery. Cytokine-stimulated interferon-? production was significantly impaired in NK cells derived from primary and revision TJRs compared with blood NK cells.NK cells are a principal tissue-infiltrating lymphocyte subset in patients with OA and patients with periprosthetic inflammation and display a quiescent phenotype that is consistent with postactivation exhaustion.

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Natural killer T cells mediate inflammation in the bile ducts.

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Natural killer T cells mediate inflammation in the bile ducts.

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