Article
Immunology
Abigail G. Harvey, Athens M. Graves, Chandana K. Uppalapati, Saoirse M. Matthews, Stephanie Rosenberg, Emma G. Parent, Madison H. Fagerlie, Jack Guinan, Brina S. Lopez, Lisa M. Kronstad
Summary: Influenza viruses cause a significant amount of disease and death. The interaction between dendritic cells (DC) and natural killer (NK) cells has been found to play an important regulatory role in T cell response during influenza infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Emily Feng, Jonathan K. Monteiro, Ana L. Portillo, Elizabeth Balint, Ali A. Ashkar
Summary: Regulation of immune responses during viral infection is critical to prevent immunopathology. NK cells not only promote viral clearance but also limit immune-mediated tissue damage. Our study reveals the immunoregulatory function of NK cells in suppressing IL-6-mediated pathogenic responses in macrophages, highlighting the potential of NK cell therapy for severe viral infections.
JOURNAL OF INFECTIOUS DISEASES
(2023)
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.
Review
Medicine, General & Internal
Ana Espino, Hicham El Costa, Julie Tabiasco, Reem Al-Daccak, Nabila Jabrane-Ferrat
Summary: The placenta is crucial for nurturing the fetus and acting as a barrier against pathogens. Early pregnancy sees expansion of specific subsets of immune cells, which play an important role in placental and fetal development.
FRONTIERS IN MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Sherri Newmyer, Marvin A. Ssemadaali, Harikrishnan Radhakrishnan, Harold S. Javitz, Parijat Bhatnagar
Summary: This study presents an engineered cell, ES-Biofactory, which can synthesize a specific protein when electrically stimulated. The cell has been used to express interferon-beta as a universal antiviral protein, and its antiviral effects on SARS-CoV-2-infected cells have been validated. The ES-Biofactory represents a promising universal antiviral cell therapy that can be quickly deployed during outbreaks and may also have applications in treating other diseases.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Takahiro Uchida, Shuhji Seki, Takashi Oda
Summary: Natural killer T (NKT) cells and NK cells have important roles in antitumor and antimicrobial functions. They are involved in various renal diseases, including acute kidney injury (AKI). NKT cells in mice are activated by specific ligands, cytokines, and bacterial components, leading to AKI. Both renal vascular endothelial cell injury (via perforin-mediated pathway) and tubular epithelial cell injury (via tumor necrosis factor-alpha/Fas ligand pathway) are independently involved in the pathogenesis of AKI. NK cells complement the functions of NKT cells in the development of infection-associated AKI. Human CD56(+) T cells, which are functional counterparts of murine NKT cells, and a subpopulation of CD56(+) NK cells damage intrinsic renal cells in vitro upon activation, possibly through mechanisms similar to those in mice. These cells are also thought to be involved in the acute exacerbation of pre-existing glomerulonephritis triggered by infection in humans, and their roles in sepsis-associated AKI are currently under investigation. In this review, we provide an overview of recent advances in the understanding of the association among infections, NKT and NK cells, and kidney injury, which is much more profound than previously considered. The important role of liver macrophages in the activation of NKT cells is also introduced.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Minna Sivonen, Katja A. Sirvio, Sara Wojciechowski, Anssi Kailaanmaki, Satu Kaipainen, Aubrey Bailey, Martin Villalba, Tuija Kekarainen
Summary: In this study, we aimed to identify the optimal activation and expansion protocol for cytotoxic NK cells against glioblastoma in vitro. The results showed that the ex vivo proliferation capacity and functionality of NK cells were affected by multiple factors, including the donor, composition of starting material, cytokine combination, and the activation protocol. These findings could be utilized for upscaling clinical NK cell manufacturing.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Joseph Gleason, Yuechao Zhao, Irene Raitman, Lin Kang, Shuyang He, Robert Hariri
Summary: The study found that adoptively transferred NK cells derived from stem cells can combat influenza A virus (IAV) infections. These cells have antiviral and anti-inflammatory properties, which can alleviate the disease burden and delay mortality. In addition, this treatment also alters immune responses, reducing inflammatory cells while increasing immune cells during viral infections. Therefore, the use of NK cell therapy for IAV infections warrants clinical investigation.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2022)
Review
Oncology
Sainiteesh Maddineni, John L. Silberstein, John B. Sunwoo
Summary: This article reviews multiple approaches for allogeneic NK cell therapy and discusses the advantages and disadvantages of each method. In recent years, NK cells have become increasingly important players in the immune response against cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Cristina Zalfa, Silke Paust
Summary: In the tumor microenvironment, myeloid-derived suppressor cells play a crucial role in regulating NK cell function, impacting the antitumor immune response. Strategies targeting MDSC-mediated immunosuppression can enhance the cytotoxic antitumor activity of NK cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Sagar N. Agnihotri, Giovanni Stefano Ugolini, Matthew Ryan Sullivan, Yichao Yang, Agustin De Ganzo, Ji Won Lim, Tania Konry
Summary: Most common cellular analysis methods employ a top-down approach, which destroys the cell and prevents correlation between genomics and functional assays. This study presents a bottom-up approach using single-cell tools, allowing functional phenotyping through observing cytotoxicity and probing underlying biology.
Article
Cell Biology
Madeline J. Lee, Michelle W. Leong, Arjun Rustagi, Aimee Beck, Leiping Zeng, Susan Holmes, Lei S. Qi, Catherine A. Blish
Summary: SARS-CoV-2 evades direct killing by natural killer (NK) cells by downregulating ligands for the activating receptor NKG2D. The viral protein Nsp1 mediates the downregulation of NKG2D ligands and alone is sufficient to confer resistance to NK cell killing.
Article
Immunology
Hillary A. Vanderven, Stephen J. Kent
Summary: Passive immunotherapies have been used for over a century to treat severe respiratory infections, but their clinical benefit for diseases like influenza and COVID-19 is still uncertain. Evidence suggests that antibody levels and extra-neutralizing antibody functions may influence the outcome of passive immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Edoardo Giussani, Andrea Binatti, Giulia Calabretto, Vanessa Rebecca Gasparini, Antonella Teramo, Cristina Vicenzetto, Gregorio Barila, Monica Facco, Alessandro Coppe, Gianpietro Semenzato, Stefania Bortoluzzi, Renato Zambello
Summary: Large granular lymphocyte leukemias (LGLL) are sustained by proliferating cytotoxic T cells or NK cells, with the etiology partly related to viral agents. Different hypotheses have been proposed regarding the role of viruses, such as the presence of Epstein Barr Virus (EBV) in aggressive NK leukemias but not in indolent CLPD-NK. New data analysis failed to identify viral sequences in CLPD-NK, suggesting a complex relationship between viral agents and NK cell activation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Luis Romero-Martin, Clara Duran-Castells, Mireia Olivella, Miriam Rosas-Umbert, Marta Ruiz-Riol, Jorge Sanchez, Dennis Hartigan-O'Connor, Beatriz Mothe, Alex Olvera, Christian Brander
Summary: This study investigates the relationship between HLA-E expression and NK cell characteristics and functions. The findings suggest that increased HLA-E expression and changes in NK subpopulations are associated with chronic HIV infection. Uncontrolled HIV infection leads to dysfunction of NK cells, loss of HLA-E regulation, and reduced viral control. The study also demonstrates the potential sensitivity of target cells presenting HIV-derived epitopes to NK lysis. However, prolonged exposure to elevated HLA-E expression levels may result in NK cell dysfunction and reduced viral control in chronic infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Immunology
Timo Rueckert, Chiara Romagnani
Summary: The transcription factor BCL11B plays a critical role in guiding NK cells along their differentiation trajectory.
SCIENCE IMMUNOLOGY
(2021)
Article
Microbiology
Hannes Vietzen, Timo Rueckert, Svenja Hartenberger, Claudia Honsig, Peter Jaksch, Silvana Geleff, Quirin Hammer, Chiara Romagnani, Maia Segura-Wang, Elisabeth Puchhammer-Stoeckl
Summary: The study reveals the complex interaction between human cytomegalovirus (HCMV) and host immune responses, particularly the interaction between HLA-E and the virus-encoded UL40 peptide, leading to a potent NK cell response and reduction in virus replication in immunosuppressed patients. Different naturally occurring HCMV-UL40 variants reduce the activation of specific host NK cells subpopulation and are associated with high-level viremia in patients, highlighting the importance of understanding these interactions in the development of severe HCMV infection and vaccine strategies.
Article
Cell Biology
Quirin Hammer, Josefine Dunst, Wanda Christ, Francesca Picarazzi, Mareike Wendorff, Pouria Momayyezi, Oisin Huhn, Herman K. Netskar, Kimia T. Maleki, Marina Garcia, Takuya Sekine, Ebba Sohlberg, Valerio Azzimato, Myriam Aouadi, Frauke Degenhardt, Andre Franke, Francesco Spallotta, Mattia Mori, Jakob Michaelsson, Niklas K. Bjorkstrom, Timo Rueckert, Chiara Romagnani, Amir Horowitz, Jonas Klingstrom, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Summary: A viral peptide encoded by the Non-structural protein 13 of SARS-CoV-2 prevents the binding of HLA-E to the inhibitory receptor NKG2A, leading to the activation of NK cells and their ability to limit viral replication. This finding provides insights into the immune response of NK cells against SARS-CoV-2 and its mechanisms.
Article
Immunology
Carla Cendon, Weijie Du, Pawel Durek, Yuk-Chien Liu, Tobias Alexander, Lindsay Serene, Xinyi Yang, Gilles Gasparoni, Abdulrahman Salhab, Karl Nordstroem, Tina Lai, Axel R. Schulz, Anna Rao, Gitta A. Heinz, Ana L. Stefanski, Anne Claussnitzer, Katherina Siewert, Thomas Doerner, Hyun-Dong Chang, Hans-Dieter Volk, Chiara Romagnani, Zhihai Qin, Sebastian Hardt, Carsten Perka, Simon Reinke, Jorn Walter, Mir-Farzin Mashreghi, Kevin Thurley, Andreas Radbruch, Jun Dong
Summary: CD4(+) T-RM cells are mobilized into the blood within 16 to 48 h after immunization with the measles-mumps-rubella (MMR) vaccine, and they make significant contribution to the systemic immune reaction.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell Biology
Johannes Steffen, Stefanie Ehrentraut, Ute Bank, Aindrila Biswas, Caio Andreeta Figueiredo, Oliver Hoelsken, Henning Peter Duesedau, Vladyslava Dovhan, Laura Knop, Jacqueline Thode, Silvina Romero-Suarez, Carmen Infante Duarte, Jason Gigley, Chiara Romagnani, Andreas Diefenbach, Christoph S. N. Klose, Thomas Schueler, Ildiko Rita Dunay
Summary: This study reveals that innate lymphoid cells (ILC1) accumulate in the brain during the onset of cerebral Toxoplasma gondii infection and contribute to the production of IFN-g and TNF, initiating a neuroinflammatory response and host defense factors.
Article
Multidisciplinary Sciences
Katja J. Jarick, Patrycja M. Topczewska, Manuel O. Jakob, Hiroshi Yano, Mohammad Arifuzzaman, Xuemei Gao, Sotiria Boulekou, Vladislava Stokic-Trtica, Pierre S. Leclere, Alexandra Preusser, Zoe A. Rompe, Anton Stamm, Amy M. Tsou, Coco Chu, Frederik R. Heinrich, Gabriela M. Guerra, Pawel Durek, Andranik Ivanov, Dieter Beule, Sofia Helfrich, Claudia U. Duerr, Anja A. Kuehl, Christina Stehle, Chiara Romagnani, Mir-Farzin Mashreghi, Andreas Diefenbach, David Artis, Christoph S. N. Klose
Summary: This article investigates the role of innate lymphoid cells (ILCs) in protective immunity. Using a mouse model specific to ILCs, researchers found that ILC2s have non-redundant functions during steady state and disease, and they interact with adaptive immune cells to organize the immune system.
Editorial Material
Multidisciplinary Sciences
Mark A. Travis, Chiara Romagnani
Summary: Active control of the immune system is necessary to prevent inflammatory bowel disease. Cell populations that promote the generation of immunosuppressive regulatory T cells in the gut have been identified.
Article
Immunology
Timo Ruckert, Caleb A. Lareau, Mir-Farzin Mashreghi, Leif S. Ludwig, Chiara Romagnani
Summary: This study reveals the clonal expansion and long-term persistence of adaptive natural killer (NK) cells in human cytomegalovirus (HCMV) infection. The NK cell clones exhibit a convergent inflammatory memory signature and specific chromatin accessibility patterns, which shape their epigenetic memory repertoire. These findings suggest the presence of adaptive mechanisms within the human innate immune system, independent of antigen-receptor diversification.
Editorial Material
Immunology
Caleb A. Lareau, Chiara Romagnani, Leif S. Ludwig
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Nils Christian Mueller, Chiara Romagnani
Summary: This review outlines the complex and diverse composition of group 1 ILC subsets in tumors, discusses how the tissue and tumor microenvironment shape their phenotype and functions, as well as describes their contrasting roles in the response to different cancers.
SEMINARS IN IMMUNOLOGY
(2022)
Review
Immunology
Pouria Momayyezi, Eleni Bilev, Hans-Gustaf Ljunggren, Quirin Hammer
Summary: This review examines immune evasion strategies employed by viruses, focusing on examples from human CMV and SARS-CoV-2. Three classes of viral evasion mechanisms are explored, including providing ligands for inhibitory receptor NKG2A, downregulating ligands for activating receptor NKG2D, and inducing immunosuppressive cytokine transforming growth factor (TGF)-β. The parallel comparison between viral and tumor immune evasion is discussed, with potential opportunities for overcoming evasion in cancer therapy. Insights gained from antiviral NK-cell responses may serve as valuable lessons for designing future cancer immunotherapies.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Brooke D. D. Huisman, Ning Guan, Timo Rueckert, Lee Garner, Nishant K. K. Singh, Andrew J. J. McMichael, Geraldine M. M. Gillespie, Chiara Romagnani, Michael E. E. Birnbaum
Summary: The authors identify peptide ligands of HLA-E that can modulate NK cell activity, including those that selectively activate NK cells.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Quirin Hammer, Angelica Cuapio, Jonna Bister, Niklas K. Bjoerkstroem, Hans-Gustaf Ljunggren
Summary: Natural killer cells play an important role in the immune response to SARS-CoV-2 infection, with early activation and changes in numbers observed. They exhibit antiviral activity against SARS-CoV-2 through direct cytotoxicity and cytokine secretion. Hyperactivation and misdirected responses of natural killer cells may contribute to the pathogenesis of COVID-19.
JOURNAL OF LEUKOCYTE BIOLOGY
(2023)
