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Review
. 2014 Apr 28;3(4):69-73.
doi: 10.1002/cld.308. eCollection 2014 Apr.

Primary biliary cirrhosis: Family, genes, and bugs

George F Mells  1
Affiliations
Review

Primary biliary cirrhosis: Family, genes, and bugs

George F Mells. Clin Liver Dis (Hoboken). .
No abstract available

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Figures

Figure 1
Figure 1
Variants associated with PBC might affect the process by which the TH1 immune response is established. Immature dendritic cells (DC) are activated by interaction of pathogen‐associated molecular patterns (PAMPs) with pattern recognition receptors (PRRs, potentially including CLEC16A). Differentiation into inflammatory DCs is promoted by pro‐inflammatory cytokines such as tumor necrosis factor, which cause increased expression of TNF, IL‐6, IL‐12, and IFN‐γ. Signaling by PRRs is mediated by NF‐κB and IRF5, and negatively regulated by RPS6KA4, while signaling by TNFRSF1A is mediated by NF‐κB and negatively regulated by DENND1B. Naïve CD4+ TH0 cells are activated by interaction of the T cell receptor (TCR) with complementary antigen, presented in the peptide binding groove of class II HLA on APCs, with costimulation by CD80 and CD86 on APC interacting with CD28 on T cells. Differentiation of the activated TH0 cell into TH1 cells is driven by IL‐12, which interacts with IL‐12R. Signals from IL‐12R are mediated by TYK2 and STAT4, which are negatively regulated by SOCS1. In turn, TH1 cells produce IFN‐γ and TGF‐β, inducing pro‐inflammatory APCs, promoting IL‐12, and suppressing IL‐4, thereby sustaining the TH1 response. Adapted with permission from Genetics of Primary Biliary Cirrhosis. Copyright 2013, John Wiley & Sons Ltd.
See this image and copyright information in PMC

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