Article
Immunology
Ratna S. Wijaya, Scott A. Read, Sakthi P. Selvamani, Stephen Schibeci, Mahmoud K. Azardaryany, Adrian Ong, David van der Poorten, Rita Lin, Mark W. Douglas, Jacob George, Golo Ahlenstiel
Summary: Direct acting antiviral therapies clear chronic hepatitis C virus (HCV) infection rapidly and restore natural killer (NK) cell function. Following HCV clearance, NK-cell memory formation involving KLRG1(+) NK cells is observed, which indicates their role in HCV clearance and potential for vaccine design.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Gastroenterology & Hepatology
Xiaohui Zhang, Yingying Jiang, Shaobin Li, Dandan Bian, Mei Liu, Ming Kong, Yu Chen, Zhongping Duan, Sujun Zheng
Summary: This study investigated the dynamic changes of natural killer (NK) cells during and after direct-acting antiviral (DAA) treatment in chronic hepatitis C patients. The study found that the cytotoxicity of NK cells showed a transient recovery in the early stage of treatment but continuously decreased below normal levels afterwards, and did not fully revert to pre-treatment levels. Additionally, alterations in NK subsets, phenotypes, and the microenvironment may be involved in these changes.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
Review
Cell Biology
Paul Kupke, Jens M. Werner
Summary: Hepatitis E virus infection is a major cause of acute hepatitis development, especially in immunocompromised patients. Current treatment options for HEV are limited, and research on the immune mechanisms involved in HEV infection is still lacking.
Article
Pharmacology & Pharmacy
Yingzhi Zhang, Shiwen Tong, Shiying Li, Xuefu Wang, Hong Ren, Wenwei Yin
Summary: NK cell activity is impaired in chronic hepatitis B (CHB) patients due to increased expression of inhibitory receptor ILT2. The level of ILT2 expression is positively correlated with viral load, and antiviral therapy can decrease ILT2 expression and restore NK cell function.
ANTIVIRAL RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Yanqin Du, Olympia E. Anastasiou, Benedikt Strunz, Janina Scheuten, Birgit Bremer, Anke Kraft, Karolina Kleinsimglinhaus, Daniel Todt, Ruth Broering, Matthias Hardtke-Wolenski, Jun Wu, Dongliang Yang, Ulf Dittmer, Mengji Lu, Markus Cornberg, Niklas K. Bjorkstrom, Tanvi Khera, Heiner Wedemeyer
Summary: The study assessed the effects of HBsAg quantities on NK cell functionality in CHB patients, finding a reshaping of the NK cell pool towards more CD56(bright) NK cells during infection. Patients with low HBsAg levels displayed an activated NK cell phenotype with defective functional responses.
LIVER INTERNATIONAL
(2021)
Article
Medicine, Research & Experimental
Priyanka Rawat, Asmita Das
Summary: NK cells play important immune functions in autoimmune diseases and successful pregnancies, providing immunity against viral infections and tumors. They are distributed in various organs and exhibit functional differences due to the regulation of transcription factors.
Article
Oncology
Seung Hee Choi, Hye Jin Kim, Joo Dong Park, Eun-Su Ko, Minwook Lee, Dae-Keum Lee, Jin-Ho Choi, Hye Jung Jang, Isaac Kim, Hae-Yun Jung, Keun-Hong Park, Kyung-Soon Park
Summary: The chemical priming of NK cells using 25KbPEI enhances their antitumor activity and migration ability, offering a simple and cost-effective method for producing therapeutic NK cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, General & Internal
Eunkyung Suh, A-Ra Cho, Ji-Hee Haam, Minchan Gil, Yun-Kyong Lee, Young-Sang Kim
Summary: This study investigated the relationship between cortisol and DHEAS serum concentrations, their ratio (CDR), and natural killer cell activity (NKA). The results showed that high levels of cortisol and CDR were associated with low NKA, while high levels of DHEAS were associated with high NKA in premenopausal women.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Alvaro Haroun-Izquierdo, Marianna Vincenti, Herman Netskar, Hanna van Ooijen, Bin Zhang, Laura Bendzick, Minoru Kanaya, Pouria Momayyezi, Shuo Li, Merete Thune Wiiger, Hanna Julie Hoel, Silje Zandstra Krokeide, Veronika Kremer, Geir Tjonnfjord, Stephanie Berggren, Kristina Wikstroem, Pontus Blomberg, Evren Alici, Martin Felices, Bjoern oenfelt, Petter Hoeglund, Bahram Valamehr, Hans-Gustaf Ljunggren, Andreas Bjoerklund, Quirin Hammer, Lise Kveberg, Frank Cichocki, Jeffrey S. Miller, Karl-Johan Malmberg, Ebba Sohlberg
Summary: This study demonstrates the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population for hematological malignancies. The expanded adaptive NK cells retained high cytotoxicity and efficiently killed leukemia cells from AML patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Pauline Rettman, Matthew D. Blunt, Rebecca J. Fulton, Andres F. Vallejo, Leidy Y. Bastidas-Legarda, Laura Espana-Serrano, Marta E. Polak, Aymen Al-Shamkhani, Christelle Retiere, Salim Khakoo
Summary: This study demonstrates the feasibility of a peptide-based KIR-targeting vaccine strategy to activate NK cells and enhance antitumor responses. The DNA vaccine upregulated genes associated with cellular metabolism and downregulated genes related to immune cell maturation. Vaccination led to enhanced antitumor responses against melanoma cells and a tumor model expressing the KIR2DS2 ligand HLA-C*0102.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Satoru Joshita, Masao Ota, Hiroyuki Kobayashi, Shun-ichi Wakabayashi, Yuki Yamashita, Ayumi Sugiura, Tomoo Yamazaki, Eiji Tanaka, Takeji Umemura
Summary: This study revealed significant associations of KIR/HLA with HCC development (KIR2DS3) and freedom from NUC therapy (KIR3DL1/HLA-Bw4) in HBV patients, although larger case studies are needed for statistical purposes.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Xiaohui Zhang, Yingying Jiang, Shaobin Li, Dandan Bian, Mei Liu, Ming Kong, Yu Chen, Zhongping Duan, Sujun Zheng
Summary: After DAA treatment, NK cell cytotoxicity initially recovers in the early stage of treatment, but then continuously decreases to below normal levels. Changes in NK cell subsets and phenotypes are closely related to NK function.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2022)
Article
Oncology
Takeji Umemura, Satoru Joshita, Hiromi Saito, Shun-ichi Wakabayashi, Hiroyuki Kobayashi, Yuki Yamashita, Ayumi Sugiura, Tomoo Yamazaki, Masao Ota
Summary: Natural killer cells, mediated through KIR-HLA interactions, play a role in hepatocellular carcinoma (HCC) development. In patients with hepatitis C virus-associated cirrhosis, the presence of HLA-Bw4 and the KIR3DL1 + HLA-Bw4 pair was significantly associated with HCC onset, suggesting a potential risk factor for HCC development in HCV cirrhosis.
Article
Genetics & Heredity
Juanjuan Huang, Tingting Zheng, Ying Liang, Ying Qin, Xing Wu, Xiaohui Fan
Summary: When tumor cells are infected by the Newcastle disease virus (NDV), the lysis of tumor cell by natural killer (NK) cells is enhanced. Transcriptome analysis of NK cells stimulated by NDV-infected hepatocellular carcinoma (HCC) cells identified 1568 differentially expressed genes (DEGs), including 1389 upregulated and 179 downregulated genes. Functional analysis revealed enrichment of DEGs in immune system, signal transmission, cell growth, cell death, and cancer pathways. Increased expression of 9 IFN family genes in NK cells upon NDV infection suggests their potential as prognosis markers for patients with HCC.
Review
Immunology
Umut Can Kucuksezer, Esin Aktas Cetin, Fehim Esen, Ilhan Tahrali, Nilgun Akdeniz, Metin Yusuf Gelmez, Gunnur Deniz
Summary: NK cells are a subset of innate lymphoid cells that play important roles in anti-tumor immune responses and immune regulation, with different subgroups showing cytotoxic functions or cytokine production. Their activation is influenced by a variety of factors, including cell surface receptors and cytokines, and their dysregulation can contribute to various immune-mediated diseases. Further research on NK cell biology and their potential therapeutic applications is necessary for better understanding and treatment of inflammatory disorders.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Michael Kriss, Lucy Golden-Mason, Jeffrey Kaplan, Faridoddin Mirshahi, V. Wendy Setiawan, Arun J. Sanyal, Hugo R. Rosen
Article
Gastroenterology & Hepatology
Nikos Stratakis, Lucy Golden-Mason, Katerina Margetaki, Yinqi Zhao, Damaskini Valvi, Erika Garcia, Lea Maitre, Sandra Andrusaityte, Xavier Basagana, Eva Borras, Mariona Bustamante, Maribel Casas, Serena Fossati, Regina Grazuleviciene, Line Smastuen Haug, Barbara Heude, Rosemary R. C. McEachan, Helle Margrete Meltzer, Eleni Papadopoulou, Theano Roumeliotaki, Oliver Robinson, Eduard Sabido, Jose Urquiza, Marina Vafeiadi, Nerea Varo, John Wright, Miriam B. Vos, Howard Hu, Martine Vrijheid, Kiros T. Berhane, David Conti, Rob McConnell, Hugo R. Rosen, Lida Chatzi
Summary: The study suggests that developmental exposure to mercury may contribute to liver injury and increased risk of NAFLD in early life.
Article
Immunology
Ana C. Maretti-Mira, Lucy Golden-Mason, Matthew P. Salomon, Mariana J. Kaplan, Hugo R. Rosen
Summary: The degree of cholesterol oxidation has different impacts on the global gene expression of human M2-like macrophages, with highly oxidized LDL causing the most dramatic changes. This oxidation also affects the function of liver and peripheral macrophages, leading to functional changes and decreased expression of important markers.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Yuchang Li, Liting Chen, Lu Li, Chantal Sottas, Stephanie K. Petrillo, Anthoula Lazaris, Peter Metrakos, Hangyu Wu, Yuji Ishida, Takeshi Saito, Lucy Golden-Mason, Hugo R. Rosen, Jeremy J. Wolff, Cristina Silvescu, Samuel Garza, Garett Cheung, Tiffany Huang, Jinjiang Fan, Martine Culty, Bangyan Stiles, Kinji Asahina, Vassilios Papadopoulos
Summary: Translocator protein (TSPO) levels increase as nonalcoholic fatty liver disease progresses from simple steatosis to nonalcoholic steatohepatitis. TSPO deficiency accelerates the progression of simple steatosis but ameliorates liver fibrosis in nonalcoholic steatohepatitis by downregulating bile acid synthesis. These findings demonstrate a dynamic and complex role for TSPO in the evolution of NAFLD.
Article
Microbiology
Matthew A. Burchill, Matthew P. Salomon, Lucy Golden-Mason, Amanda Wieland, Ana C. Maretti-Mira, Michael Gale, Hugo R. Rosen
Summary: Chronic HCV infection leads to dysregulation of innate immune responses and impaired T cell function. DAA therapy can induce significant changes in gene expression in T cells, offering a valuable data source to investigate the effects of DAA treatment on T cell populations.
Article
Transplantation
Jordan Nichols, Philip Vutien, James Perkins, Scott W. Biggins, Andre A. S. Dick, Stacey McCandlish, Kiran Bambha, Jorge Reyes
Summary: This study aimed to investigate whether the Liver Disease Health-Related Quality of Life Short Form or the Area Deprivation Index could help identify liver transplant candidates at risk of delisting due to nonadherence. The results showed that poor memory and poor future outlook, as indicated by the responses on the Liver Disease Health-Related Quality of Life Short Form, were associated with increased risk of wait list removal due to nonadherence.
EXPERIMENTAL AND CLINICAL TRANSPLANTATION
(2022)
Article
Multidisciplinary Sciences
Lauriane Galle-Treger, Doumet Georges Helou, Christine Quach, Emily Howard, Benjamin P. Hurrell, German R. Aleman Muench, Pedram Shafiei-Jahani, Jacob D. Painter, Andrea Iorga, Lily Dara, Juliet Emamaullee, Lucy Golden-Mason, Hugo R. Rosen, Pejman Soroosh, Omid Akbari
Summary: This study shows that disruption of the autophagy pathway in CD11c(+) cells accelerates the development of non-alcoholic fatty liver disease (NAFLD) in mice. The production of IL-23 by hepatic CD11c(+) cells plays a role in NAFLD pathogenesis, and blocking IL-23 can reduce the disease. These findings provide insights into the function of autophagy and IL-23 production in NAFLD, and suggest potential therapeutic targets.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Ana C. Maretti-Mira, Matthew P. Salomon, Angela M. Hsu, Gary C. Kanel, Lucy Golden-Mason
Summary: This study found that the dietary cholesterol content directly affects the gene expression of hepatic macrophages. Prolonged high cholesterol intake induces long-lasting hepatic damage and expands a dysfunctional pro-fibrotic restorative macrophage population even after cholesterol reduction.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Lei W. Yu, Shirley N. Paski, Jennifer Dodge, Kiran Bambha, Scott Biggins, George Ioannou
Summary: Supplementing with branched chain amino acids (BCAA) may not have a significant impact on liver-related mortality in patients with advanced fibrosis or compensated cirrhosis. A retrospective cohort study showed no association between long-term dietary intake of BCAA and liver-related death or transplantation in HCV-infected patients. BCAA intake was also not associated with the risk of hepatocellular carcinoma, encephalopathy, or clinical hepatic decompensation.
Article
Surgery
Catherine E. Kling, Scott W. Biggins, Kiran M. Bambha, Lauren D. Feld, John H. Perkins, Jorge D. Reyes, James D. Perkins
Summary: Small waitlist candidates have a disadvantage in receiving liver transplants compared to larger candidates. Prioritizing the allocation of smaller liver donors to smaller candidates may help overcome this disparity.
Article
Immunology
Ana C. Maretti-Mira, Matthew P. Salomon, Angela M. Hsu, Lily Dara, Lucy Golden-Mason
Summary: The natural killer (NK) cell population in the liver plays a critical role in innate immunity, and its functions are influenced by the surrounding environment. In the late stage of fibrosis, NK cells become dysfunctional, but the impact of disease etiology on NK cell behavior during cirrhosis is unclear. Using single-cell RNA sequencing (scRNA-seq), this study characterized hepatic NK cells in end-stage cirrhotic livers from subjects with different liver diseases, showing that disease etiology affects hepatic NK cell heterogeneity. Therapeutic strategies targeting NK cells for fibrosis prevention or treatment should consider the specific liver disease etiology.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Kiran Bambha, Nicole J. Kim, Mark Sturdevant, James D. Perkins, Catherine Kling, Ramasamy Bakthavatsalam, Patrick Healey, Andre Dick, Jorge D. Reyes, Scott W. Biggins
Summary: By analyzing OPTN living donor liver transplant (LDLT) data, we constructed random forest survival models to predict 10-year graft survival for different types of liver transplants. The ratio of body surface area between donor and recipient was an important predictor in all models, along with factors such as malignant diagnosis, medical location at LDLT, and moderate ascites. These predictive models can assist in identifying and stratifying potential recipients for hepatic grafts while considering complex donor-recipient interactions.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Medicine, General & Internal
J. Nichols, P. Vutien, S. Biggins, A. Dick, S. McCandlish, K. Bambha, J. Reyes, J. D. Perkins
JOURNAL OF INVESTIGATIVE MEDICINE
(2022)
Meeting Abstract
Gastroenterology & Hepatology
Catherine Kling, Brian Cook, Scott W. Biggins, Kiran Bambha, Jorge D. Reyes, John Perkins, James D. Perkins
Meeting Abstract
Surgery
K. Bambha, J. Perkins, M. Sturdevant, S. W. Biggins, R. Bakthavatsalam, P. Healey, A. Dick, J. Reyes
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)