scholarly journals Biliary Innate Immunity: Function and Modulation

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Kenichi Harada ◽  
Yasuni Nakanuma
Keyword(s):  
Innate Immunity ◽  
Epithelial Cells ◽  
Biliary Atresia ◽  
Th17 Cells ◽  
Bile Ducts ◽  
Innate Immune ◽  
Negative Regulator ◽  
Biliary Cirrhosis ◽  
Mesenchymal Transition ◽  
Biliary Epithelial Cells

Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with primary biliary cirrhosis (PBC) and biliary atresia. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). Tolerance to bacterial PAMPs such as lipopolysaccharides is also important to maintain homeostasis in the biliary tree, but tolerance to double-stranded RNA (dsRNA) is not found. In PBC, CD4-positive Th17 cells characterized by the secretion of IL-17 are implicated in the chronic inflammation of bile ducts and the presence of Th17 cells around bile ducts is causally associated with the biliary innate immune responses to PAMPs. Moreover, a negative regulator of intracellular TLR signaling, peroxisome proliferator-activated receptor-γ(PPARγ), is involved in the pathogenesis of cholangitis. Immunosuppression using PPARγligands may help to attenuate the bile duct damage in PBC patients. In biliary atresia characterized by a progressive, inflammatory, and sclerosing cholangiopathy, dsRNA viruses are speculated to be an etiological agent and to directly induce enhanced biliary apoptosis via the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Moreover, the epithelial-mesenchymal transition (EMT) of biliary epithelial cells is also evoked by the biliary innate immune response to dsRNA.

scholarly journals Innate immune response to double-stranded RNA in biliary epithelial cells is associated with the pathogenesis of biliary atresia

Hepatology ◽  
2007 ◽  
Vol 46 (4) ◽  
pp. 1146-1154 ◽  
Author(s):  
Kenichi Harada ◽  
Yasunori Sato ◽  
Keita Itatsu ◽  
Kumiko Isse ◽  
Hiroko Ikeda ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Biliary Atresia ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Double Stranded Rna ◽  
Biliary Epithelial Cells

Epithelial-mesenchymal transition induced by biliary innate immunity contributes to the sclerosing cholangiopathy of biliary atresia

2009 ◽  
Vol 217 (5) ◽  
pp. 654-664 ◽  
Author(s):  
Kenichi Harada ◽  
Yasunori Sato ◽  
Hiroko Ikeda ◽  
Kumiko Isse ◽  
Satoru Ozaki ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Biliary Atresia ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

TLR2-mediated innate immune priming boosts lung anti-viral immunity

2020 ◽  
pp. 2001584
Author(s):  
Jason Girkin ◽  
Su-Ling Loo ◽  
Camille Esneau ◽  
Steven Maltby ◽  
Francesca Mercuri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immunity ◽  
Viral Load ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Immune Priming ◽  
Tlr2 Activation

Research questionAssessment of whether TLR2 activation boosts the innate immune response to rhinovirus infection, as a treatment strategy for virus-induced respiratory diseases.MethodsWe employed treatment with a novel TLR2 agonist (INNA-X) prior to rhinovirus infection in mice, and INNA-X treatment in differentiated human bronchial epithelial cells derived from asthmatic-donors. We assessed viral load, immune cell recruitment, cytokines, type I and III IFN production, as well as the lung tissue and epithelial cell immune transcriptome.ResultsWe show in vivo, that a single INNA-X treatment induced innate immune priming characterised by low-level IFN-λ, Fas ligand, chemokine expression and airway lymphocyte recruitment. Treatment 7-days before infection significantly reduced lung viral load, increased IFN-β/λ expression and inhibited neutrophilic inflammation. Corticosteroid treatment enhanced the anti-inflammatory effects of INNA-X. Treatment 1-day before infection increased expression of 190 lung tissue immune genes. This tissue gene expression signature was absent with INNA-X treatment 7-days before infection, suggesting an alternate mechanism, potentially via establishment of immune cell-mediated mucosal innate immunity. In vitro, INNA-X treatment induced a priming response defined by upregulated IFN-λ, chemokine and anti-microbial gene expression that preceded an accelerated response to infection enriched for NF-κB-regulated genes and reduced viral loads, even in epithelial cells derived from asthmatic donors with intrinsic delayed anti-viral immune response.ConclusionAirway epithelial cell TLR2 activation induces prolonged innate immune priming, defined by early NF-κB activation, IFN-λ expression and lymphocyte recruitment. This response enhanced anti-viral innate immunity and reduced virus-induced airway inflammation.

Connective tissue growth factor expression is increased in biliary epithelial cells in biliary atresia

2005 ◽  
Vol 40 (11) ◽  
pp. 1721-1725 ◽  
Author(s):  
Michael R. Narkewicz ◽  
Arvind Kasaragod ◽  
M. Scott Lucia ◽  
Sean Pflummer ◽  
Ronald J. Sokol ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Connective Tissue ◽  
Biliary Atresia ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Biliary Epithelial Cells ◽  
Factor Expression ◽  
Growth Factor Expression
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