Increased cd1d expression on small bile duct epithelium and epithelioid granuloma in livers in primary biliary cirrhosis

Tsuneyama, Koichi; Yasoshima, Mitsue; Harada, Kenichi; Hiramatsu, Katsushi; Gershwin, M. Eric; Nakanuma, Yasuni

doi:10.1002/hep.510280303

Cited by 97 publications

(73 citation statements)

References 30 publications

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“…80,84 CD1d is expressed at very low levels in healthy human as well as rodent hepatocytes, 7,30,31 but increases markedly on epithelioid granuloma cells in PBC. 81 CD1d is expressed on cholangiocytes and epithelial cells of the small bile ducts in earlier stage PBC and is lost in the late stages. A subsequent study demonstrated that CD3 ϩ /CD57 ϩ cells are increased in the portal tracts, in particular around the interlobular bile ducts, in patients with PBC.…”

Section: Role In Liver Diseasementioning

confidence: 99%

“…Focal CD1d staining was increased on cholangiocytes and inflammatory cells in chronic HCV infection, 56 as previously described in PBC. 80,81 Furthermore, nonclassical variant CD1d-reactive T cells were found in uninfected livers, although they were found more frequently in HCV-infected donors. Although CD1d-reactive T cells from mild cases had a strong Th1 bias, Th2 cytokines were also produced in advanced fibrosis and cirrhosis.…”

Section: Role In Infections Of the Livermentioning

confidence: 99%

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To be or not to be NKT: Natural killer T cells in the liver

2004

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N KT cells are a diverse group of cells that share features of both classical T cells and natural killer (NK) cells, and have similarly diverse functions. One of the complexities in understanding NKT cells involves sorting through the various terminology that has been applied to them in the emerging literature. 1,2 Functionally, a major subset of these cells are defined by reactivity against CD1d, which is one of five known glycolipid-binding nonpolymorphic major histocompatibility complex class 1-like glycoproteins: CD1a through e. 3 These glycoproteins appear to have evolved to facilitate recognition of nonprotein antigens-specifically glycolipid antigens, including those present in the cell walls of mycobacterial species. CD1d is constitutively expressed on a number of hematopoietic-derived antigenpresenting cell (APC) types-including B cells and myeloid cells-and can be expressed by human T cells as well as healthy hepatocytes. Physiological ligands for CD1d remain poorly defined, although both glycolipids and hydrophobic peptides bind to CD1 family molecules. 4,5 Most antigen studies have used the synthetic glycolipid ␣-galactosylceramide (␣GalCer), which binds to CD1d and activates a specific subset of both murine and human NKT cells in vitro and in vivo. 5,6 CD1d is remarkably conserved across mammalian species, with mouse and human CD1d having greater than 90% sequence homology. 7 Consequently, murine CD1d-reactive T cells recognize human CD1d, and vice versa. 8 After activation, NKT cells are highly versatile and can produce large amounts of interferon gamma (IFN-␥) and interleukin (IL)-4 9,10 as prototypic type 1 and type 2 cytokines, respectively, as well as display NK/lymphokine-activated killing-like FasL-mediated or perforin-dependent CD1d-specific cytotoxicity 11-14 thus potentially contributing to protective and pathogenic responses against multiple infectious agents and tumors.CD1d is expressed by dendritic cells (DCs), and ␣Gal-Cer-loaded DCs mediate activation of invariant NKT cells. [15][16][17][18] Although peripheral NKT cells can recognize and respond to other CD1d ϩ cells, their in vivo activation may be initiated by interactions with DCs and possibly B cells. The interactions between invariant NKT cells and DCs share many features of interactions between conventional CD4 ϩ T cells and DCs. DCs pulsed with ␣GalCer stimulate NKT cells through T cell receptor (TCR) ligation. 2,19,20 NKT cell activation and IFN-␥ production are markedly enhanced by DC-produced IL-12, with an increase in the IL-12 receptor on activated NKT cells. 15,21,22 Conversely, invariant NKT cells also interact with ␣Gal-Cer-loaded DCs to enhance CD4 ϩ and CD8 ϩ T-cell responses 16,17,23,24 and with B cells to provide help for antibody production. 25 However, ␣Galcer is not a physiological antigen, and it is not yet clear whether physiological NKT-DC interactions are mediated by specific CD1d-presented antigens or are antigen independent.The classical CD1d-reactive NKT cell population expresses a highly restricted TCR r...

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Section: Role In Liver Diseasementioning

confidence: 99%

Section: Role In Infections Of the Livermentioning

confidence: 99%

To be or not to be NKT: Natural killer T cells in the liver

2004

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“…Previous studies described the profiles of inflammatory cells surrounding bile ducts in PBC (9,(14)(15)(16)(17). Cellular profiles may change depending on the process of biliary inflammation.…”

Section: Immunopathological Characteristics Of Damaged Biliary Epithementioning

confidence: 99%

Primary Biliary Cholangitis: Its Pathological Characteristics and Immunopathological Mechanisms

et al. 2017

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: Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is an organ-specific autoimmune disease that predominantly affects middle-aged women and is characterized by the chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and, ultimately, fibrosis. The serological hallmark of PBC is the presence of anti-mitochondrial autoantibodies (AMA). Several mechanisms have been proposed for immune-mediated bile duct damage in PBC, including the roles of T cells, B cells, other cell phenotypes, and AMA. A sign of fragility of biliary epithelial cells caused by apoptosis, senescence, and autophagy has also been noted. Several complex steps and mechanisms appear to be involved in the induction and progression of cholangitis and biliary degeneration in patients with PBC.

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“…Recent studies have demonstrated that CD1d1 expression is up-regulated in response to some infections or inflammatory conditions. For example, increased CD1d1 expression can be detected on mucosal-associated B cells after the development of intestinal inflammation (30) and on biliary hepatocytes during hepatitis C virus infection (31). These findings suggest that the levels and cell type-specific expression of CD1d1 may affect the functions of iNKT cells.…”

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confidence: 92%

Transcriptional Regulation ofCD1D1by Ets Family Transcription Factors

Geng

Laslo

Barton

et al. 2005

The Journal of Immunology

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CD1 molecules are MHC class I-like glycoproteins specialized in presenting lipid/glycolipid Ags to T cells. The distinct cell-type specific expression of CD1D1 plays an important role in the development and function of NKT cells, a unique subset of immunoregulatory T cells. However, the mechanisms regulating CD1D1 expression are largely unknown. In this study, we have characterized the upstream region of the CD1D1 gene and identified a minimal promoter region within 200 bp from the translational start site of CD1D1 that exhibits cell-type specific promoter activity. Analysis of this region revealed an Ets binding site critical for CD1D1 promoter activity. Gel shift assays and chromatin immunoprecipitation experiments showed that Elf-1 and PU.1 bind to the CD1D1 promoter. Furthermore, we found that gene disruption of Elf-1 resulted in decreased CD1D1 expression on B cells but not other cell types, whereas conditional activation of PU.1 negatively regulated CD1D1 expression in PU.1-deficient myeloid cells. These findings are the first to demonstrate that Ets proteins are involved in the transcriptional regulation of CD1D1 and that they may function uniquely in different cell types.

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Increased cd1d expression on small bile duct epithelium and epithelioid granuloma in livers in primary biliary cirrhosis

Cited by 97 publications

References 30 publications

To be or not to be NKT: Natural killer T cells in the liver

To be or not to be NKT: Natural killer T cells in the liver

Primary Biliary Cholangitis: Its Pathological Characteristics and Immunopathological Mechanisms

Transcriptional Regulation ofCD1D1by Ets Family Transcription Factors

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