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Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis
Abstract
Although the pathogenesis of primary biliary cirrhosis (PBC) remains enigmatic, the immune system plays a key role in the initiation and subsequent development of pathology. Previous studies have indicated a critical role of the innate immune system. Importantly, natural killer (NK) cells are abundant in liver where they serve as sentinels of the immune system. In addition, NK cells have significant biologic activity based on their production of immunoregulatory cytokines. To address this issue, we have investigated several qualitative and quantitative activities of NK cells in patients with PBC as well as normal and liver diseased controls. We report herein a marked increase in the frequency and absolute number of blood and liver NK cells in PBC patients. Moreover, the cytotoxic activity and perforin expression by isolated NK cells were significantly increased in PBC patients associated with increased levels of plasma IL-8 and the expression of CD128a (IL-8 receptor) on NK cells. In contrast, the levels of IFN-gamma, IL-6 and IL-8 synthesized by NK cells were significantly decreased in PBC patients as compared to controls. In conclusion, data from this study provide compelling evidence supporting a biologic role of NK cells in the immunopathogenesis of PBC.
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“including natural killer cells and myeloid-derived suppressor cells, has been observed in patients with primary biliary cholangitis.[41][42][43][44]”
From Primary biliary cholangitis. (2024) · cites this paper as [41]
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Metadata
- Authors
- Chuang, Y.-H., Lian, Z.-X., Tsuneyama, K., Chiang, B.-L., Ansari, A. A., Coppel, R. L., & Eric Gershwin, M.
- Affiliations
- University of California, Davis (US)
- University of Toyama (JP)
- National Taiwan University (TW)
- Emory University (US)
- Monash University (AU)
- Venue
- Journal of Autoimmunity
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 26
- Issue
- 4
- Pages
- 232-240
- ISSN
- 0896-8411 (ISSN-L)
- OpenAlex
- W2013215038
- Cited by
- 121
- References
- 48
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 9 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 8 · 2014: 8 · 2013: 9 · 2012: 7
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Autoimmunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of California, Davis
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 39588, N01 DK-92310)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- primary biliary cirrhosis, natural killer cells, NK cell cytotoxicity, perforin, interleukin-8, interferon-gamma, interleukin-6, cytokine production, innate immunity
- MeSH terms
- Adult, Aged, Female, Humans, Immunity, Innate, Interferon-gamma, Killer Cells, Natural, Liver Cirrhosis, Biliary, Male, Membrane Glycoproteins, Middle Aged, Poly I-C, Interleukin-6, Cytokines, Interleukin-8, Receptors, Interleukin-8A, Pore Forming Cytotoxic Proteins, Perforin
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