Article
Oncology
Lei Zhan, Junhui Zhang, Jing Zhang, Xiaojing Liu, Suding Zhu, Yuchuan Shi, Yu He, Wenyan Wang, Yijing Wei, Zhenhai Tang, Guo Chen, Bing Wei, Yunxia Cao
Summary: In this study, the researchers found that upregulated autophagy and decreased expression of MHC-I and NLRC5 were associated with endometrial cancer (EC). Inhibition of autophagy was found to suppress MHC-I gene expression. They also discovered that LC3 interacted with NLRC5 to inhibit the NLRC5-mediated MHC-I antigen presentation pathway. These findings suggest that inhibiting LC3 and promoting NLRC5 may be a promising immunotherapy strategy for EC management.
Review
Biochemistry & Molecular Biology
Akhil Shukla, Maryse Cloutier, Madanraj Appiya Santharam, Sheela Ramanathan, Subburaj Ilangumaran
Summary: The immune system constantly monitors and eliminates cancerous cells, with CD8(+) cytotoxic T lymphocytes playing a key role in tumor cell killing. Cancer cells evade immune surveillance by downregulating MHC-I and key proteins of the antigen processing and presentation machinery. NLRC5 has been identified as the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of NLRC5 are common causes of MHC-I defects in cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Richel J. C. Bilderbeek, Maksim V. Baranov, Geert van den Bogaart, Frans Bianchi
Summary: This study reveals the over-presentation of membrane protein fragments in cytolytic and helper T cell responses. It also demonstrates the evolutionary conservation and lower frequency of mutations in transmembrane helices, suggesting that T cells are more tuned to respond to membrane proteins to avoid evasion by pathogens.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Madanraj Appiya Santharam, Akhil Shukla, Dominique Levesque, Thomas A. Kufer, Francois-Michel Boisvert, Sheela Ramanathan, Subburaj Ilangumaran
Summary: Aggressive tumors avoid immune attack by suppressing MHC-I expression. NLRC5 is a transcriptional activator of MHC-I, and defects in NLRC5 result in MHC-I defects. Restoring NLRC5 expression in poorly immunogenic B16 melanoma cells induces MHC-I and antitumor immunity, suggesting the potential use of NLRC5 for tumor immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Xiang Liu, Lingdan Yin, Mei Xue, Jianfei Chen, Liang Li, Fang Fu, Li Feng, Pinghuang Liu
Summary: It was found that porcine deltacoronavirus (PDCoV) infection upregulated the expression of porcine MHC-I molecules and associated genes, but not MHC-II molecules. This upregulation was mediated through the enhancement of NLRC5 expression by PDCoV, which was regulated by RIG-I-initiated type I interferon signaling pathway and IRF1. These findings provide insights into the manipulation of MHC molecules by PDCoV and may have implications for the development of therapies and vaccines against PDCoV.
JOURNAL OF VIROLOGY
(2022)
Letter
Oncology
Tamara Steinfass, Juliane Poelchen, Qian Sun, Giovanni Mastrogiulio, Daniel Novak, Marlene Vierthaler, Sandra Pardo, Aniello Federico, Laura Hueser, Thomas Hielscher, Rafael Carretero, Rienk Offringa, Peter Altevogt, Viktor Umansky, Jochen Utikal
Summary: Melanoma is a deadly form of skin cancer with increasing incidence. Understanding the underlying mechanisms of resistance to treatment can enhance therapy efficacy and success.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
Article
Immunology
Yanan Wu, Nianzhi Zhang, Keiichiro Hashimoto, Chun Xia, Johannes M. Dijkstra
Summary: The structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar, but there are differences in the components. Comparative analysis of primitive vertebrate species' pMHC-I and pMHC-II structures sheds light on the evolution of MHC structures. The establishment of pMHC-I involved the development of important new functions that have been well conserved since their early inception.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Steven X. Cho, Saptha Vijayan, Ji-Seung Yoo, Toshiyuki Watanabe, Ryota Ouda, Ning An, Koichi S. Kobayashi
Summary: The presentation of antigenic peptides by MHC class I and class II molecules is crucial for activating the adaptive immune system, with CIITA and NLRC5 serving as the major transcriptional activators of MHC class II and class I gene expression. Recent advances in understanding the role of NLRC5 in infectious diseases and cancer have shed light on its biological significance and mechanism in MHC class I expression.
Article
Biochemistry & Molecular Biology
Chrissie E. B. Ong, Yuanyuan Cheng, Hannah V. Siddle, A. Bruce Lyons, Gregory M. Woods, Andrew S. Flies
Summary: MHC-I and MHC-II molecules play critical roles in antigen presentation and T cell immunity. Two transmissible devil facial tumours (DFT1 and DFT2) exploit the MHC-I pathway to overcome immune and allogeneic barriers. This study reveals that overexpression of NLRC5 regulates the MHC-I pathway and raises interest in the expression of MHC-II in tumor cells. This finding has important implications for immunotherapy and cancer vaccine research.
Article
Cell Biology
Martin Plasil, Jan Oppelt, Marie Klumplerova, Jana Bubenikova, Leona Vychodilova, Eva Janova, Karla Stejskalova, Jan Futas, Ales Knoll, Agnes Leblond, Andrei D. Mihalca, Petr Horin
Summary: The major histocompatibility complex (MHC) includes class I and II genes that are vital for immune response against pathogens. These genes exhibit high levels of single nucleotide polymorphisms (SNPs) in exons encoding antigen binding sites. This study aimed to investigate the variability of MHC genes, particularly MHC class I physical haplotypes. Using long-range next-generation sequencing, alleles in exon 2 and exon 3 were identified in three genetically distinct horse breeds. A total of 116 allelic variants were found in the MHC class I genes, with 112 being novel. Extensive variability in the MHC region was confirmed, and diversifying and purifying selection were detected in the analyzed MHC class I and II loci.
Article
Multidisciplinary Sciences
Sayuri Yoshihama, Steven X. Cho, Jason Yeung, Xuedong Pan, Gregory Lizee, Kranti Konganti, Valen E. Johnson, Koichi S. Kobayashi
Summary: The expression of NLRC5 and MHC class I-related genes is crucial for the effective response of melanoma patients to anti-CTLA-4 and anti-PD1 checkpoint blockade immunotherapy, serving as potential predictive biomarkers for prognosis and treatment response.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Shan Chen, Yuqing Xu, Yeqing Qian, Zhaohui Li, Minyue Dong
Summary: This study identified a genetic mutation associated with severe immunodeficiency and demonstrated its pathogenicity through experimental validation. This research has important implications for genetic counseling, prenatal diagnosis, and preimplantation genetic testing for immunodeficiency.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
Yingying Shi, Yu Liu, Jiaxin Huang, Zhenyu Luo, Xuemeng Guo, Mengshi Jiang, Xiang Li, Yichao Lu, Xu Liu, Xinyu Shan, Lihua Luo, Jian You
Summary: This study indicates that a simultaneous and coordinated mobilization of MHC-restricted immunity may enhance cancer therapy, providing new insights for cancer treatment.
Article
Multidisciplinary Sciences
Binkai Chi, Muhammet M. Oeztuerk, Christina L. Paraggio, Claudia E. Leonard, Maria E. Sanita, Mahtab Dastpak, Jeremy D. O'Connell, Jordan A. Coady, Jiuchun Zhang, Steven P. Gygi, Rodrigo Lopez-Gonzalez, Shanye Yin, Robin Reed
Summary: Mutations in RNA/DNA-binding proteins can cause ALS, but the exact disease mechanisms are still unclear. This study found that a group of ALS-associated proteins can affect the expression of genes involved in the MHC II antigen presentation pathway. Additionally, hematopoietic progenitor cells with mutations also exhibit disrupted MHC II expression. These findings suggest that the loss of the MHC II pathway may result in the immune system's failure to protect motor neurons from ALS-related damage.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Chrissie E. B. Ong, Amanda L. Patchett, Jocelyn M. Darby, Jinying Chen, Guei-Sheung Liu, A. Bruce Lyons, Gregory M. Woods, Andrew S. Flies
Summary: The downregulation of MHC-I is a common immune evasion strategy in many cancers, including two allogeneic clonal transmissible cancers that have affected Tasmanian devils. This study revealed that NLRC5 plays a major role in regulating MHC-I in devils, and suggests that MHC-I could be a target for anti-tumor and allogeneic immunity. Potential immunotherapy and vaccine targets for protecting devils from transmissible cancers could include NLRC5.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ioannis Kienes, Tanja Weidl, Nora Mirza, Mathias Chamaillard, Thomas A. Kufer
Summary: Type I interferon signaling is crucial for immune responses to viruses, fungi, or bacteria, but the amplitude and timing of the response are also key to preventing inadequate outcomes or tissue damage. NLRs, a family of proteins capable of sensing microbial products and signals related to tissue injury, regulate the quality of interferon signaling. Current understanding of the function of NLRs in type I interferon responses is incomplete, but they play important roles in influencing the immune response to viral infections and the development of autoimmunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Gang Pei, Joanna Zyla, Lichun He, Pedro Moura-Alves, Heidrun Steinle, Philippe Saikali, Laura Lozza, Natalie Nieuwenhuizen, January Weiner, Hans-Joachim Mollenkopf, Kornelia Ellwanger, Christine Arnold, Mojie Duan, Yulia Dagil, Mikhail Pashenkov, Ivo Gomperts Boneca, Thomas A. Kufer, Anca Dorhoi, Stefan H. E. Kaufmann
Summary: This study revealed the role of NOD1/2 in monitoring cellular homeostasis by sensing the intracellular metabolite S1P, which acts as a novel activator for NOD1/2, and NOD1/2 as molecular hubs that integrate bacterial and metabolic signals.
Article
Immunology
Ioannis Kienes, Sarah Bauer, Clarissa Gottschild, Nora Mirza, Jens Pfannstiel, Martina Schroeder, Thomas A. Kufer
Summary: The study reveals that NLRP11 plays a role in regulating type I IFN induction during viral infection and controls NLRP3 inflammasome activation by binding to DDX3X. NLRP11 abolishes IKK epsilon-mediated phosphorylation of DDX3X, leading to reduced type I IFN induction upon viral infection. By interacting with DDX3X through the LRR domain, NLRP11 suppresses NLRP3-mediated inflammasome activation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Heidrun Steinle, Kornelia Ellwanger, Nora Mirza, Selina Briese, Ioannis Kienes, Jens Pfannstiel, Thomas A. Kufer
Summary: The study identified the molecular composition of the complexes formed by RIPK2 with several cellular proteins upon NOD1/2 activation. These interactions were validated using protein binding assays and immunofluorescence staining. Besides bacterial activation of NOD1/2, RIPK2 cytosolic complexes were also formed following XIAP inhibition and treatment with RIPK2 inhibitors.
JOURNAL OF CELL SCIENCE
(2021)
Review
Immunology
Ioannis Kienes, Ella L. Johnston, Natalie J. Bitto, Maria Kaparakis-Liaskos, Thomas A. Kufer
Summary: This article summarizes the subversion strategies used by bacterial pathogens to evade host immune detection, focusing on the well-studied NLRs NOD1/2, NLRP3, and NLRC4. The authors discuss how bacterial pathogens activate these NLRs to promote inflammation and disease, as well as mechanisms used by bacteria to attenuate NLR activation and interfere with host immunity. They also highlight the role of NLRs in facilitating immunotolerance and persistence of bacteria in the host, and the therapeutic potential of harnessing bacterial immune subversion strategies for chronic inflammatory conditions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Subhash Mehto, Kautilya Kumar Jena, Rina Yadav, Swatismita Priyadarsini, Pallavi Samal, Sivaram Krishna, Kollori Dhar, Ashish Jain, Nishant Ranjan Chauhan, Krushna C. Murmu, Ramyasingh Bal, Rinku Sahu, Pundrik Jaiswal, Bhabani Sankar Sahoo, Srinivas Patnaik, Thomas A. Kufer, Tor Erik Rusten, Swati Chauhan, Punit Prasad, Santosh Chauhan
Summary: This study reveals a unique mechanism where bacterial infection induces the formation of endogenous RIPK2 oligomers (RIPosomes) that coat the bacteria to induce NF-kappa B response. Autophagy proteins IRGM and p62/SQSTM1 physically interact with NOD1/2, RIPK2 and RIPosomes to promote their selective autophagy and limit NF-kappa B activation. This study highlights the involvement of innate immune proteins and autophagy machinery in bacterial defense and immune homeostasis maintenance.
Article
Food Science & Technology
Felipe Jimenez-Aspee, Jonas Pospiech, Sarah Bauer, Nadine Sus, Thomas A. Kufer, Jan Frank
Summary: This study evaluated the bioaccessibility and transepithelial transport of 20E in P.andina fruit, as well as the activation of selected nuclear receptors in human cells after simulated digestion. The results showed that components other than 20E in the fruit extract are responsible for the effects on LXR-α and -β. This finding suggests the potential role of P.andina fruit in cholesterol metabolism and inflammatory diseases.
MOLECULAR NUTRITION & FOOD RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Madanraj Appiya Santharam, Akhil Shukla, Dominique Levesque, Thomas A. Kufer, Francois-Michel Boisvert, Sheela Ramanathan, Subburaj Ilangumaran
Summary: Aggressive tumors avoid immune attack by suppressing MHC-I expression. NLRC5 is a transcriptional activator of MHC-I, and defects in NLRC5 result in MHC-I defects. Restoring NLRC5 expression in poorly immunogenic B16 melanoma cells induces MHC-I and antitumor immunity, suggesting the potential use of NLRC5 for tumor immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Sarah Bauer, Lucy Hezinger, Fjolla Rexhepi, Sheela Ramanathan, Thomas A. Kufer
Summary: Obesity and its associated metabolic morbidities, fueled by low-grade inflammation primarily from adipose tissue, pose a major challenge to healthcare systems worldwide. Nucleotide-binding and oligomerization domain (NLR) family proteins have been found to play a crucial role in the development and control of obesity and obesity-associated inflammatory responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Tomasz Prochnicki, Matilde B. Vasconcelos, Kim S. Robinson, Matthew S. J. Mangan, Dennis De Graaf, Kateryna Shkarina, Marta Lovotti, Lena Standke, Romina Kaiser, Rainer Stahl, Fraser G. Duthie, Maximilian Rothe, Kateryna Antonova, Lea-Marie Jenster, Zhi Heng Lau, Sarah Roesing, Nora Mirza, Clarissa Gottschild, Dagmar Wachten, Claudia Guenther, Thomas A. Kufer, Florian I. Schmidt, Franklin L. Zhong, Eicke Latz
Summary: NLRP10 can assemble an inflammasome upon mitochondrial damage and is highly expressed in differentiated keratinocytes. It monitors mitochondrial integrity in an mtDNA-independent manner, suggesting the recognition of distinct molecular entities displayed by the damaged organelles.
Editorial Material
Immunology
Uday Kishore, Thomas A. Kufer
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Himadri B. B. Thapa, Paul Kohl, Franz G. G. Zingl, Dominik Fleischhacker, Heimo Wolinski, Thomas A. A. Kufer, Stefan Schild
Summary: The release of membrane vesicles from bacteria plays an important role in intra- and interspecies communication. Although the immunomodulatory properties of bacterial membrane vesicles (MVs) have been recognized, their interactions with host cells and underlying signaling pathways are not well understood. This study provides a comparative analysis of the proinflammatory cytokine response of human intestinal epithelial cells to MVs derived from different gut bacteria. The results show that outer membrane vesicles (OMVs) from Gram-negative bacteria induce a stronger proinflammatory response than MVs from Gram-positive bacteria, and the immunomodulatory activities vary between different species.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Sarah Bauer, Vanessa Aeissen, Alena M. Bubeck, Ioannis Kienes, Kornelia Ellwanger, Mona Scheurenbrand, Fjolla Rexhepi, Sheela Ramanathan, Philip Rosenstiel, W. Florian Fricke, Thomas A. Kufer
Summary: Nucleotide-binding and oligomerization domain containing 5 (NLRC5) is a transcriptional regulator of major histocompatibility (MHC) class I genes. Its role extends beyond MHC genes, as it is also involved in metabolic traits. In this study, we found that NLRC5 contributes to weight gain in mice fed a high-fat diet (HFD) by enhancing the expression of peroxisome proliferator-activated receptor (PPAR) gamma target genes. We also identified two novel interaction partners of NLRC5, Sin3A and negative elongation factor (NELF) B, which partly modulate NLRC5's transcriptional effect.
Article
Multidisciplinary Sciences
L. S. Tran, L. Ying, K. D'Costa, G. Wray-McCann, G. Kerr, L. Le, C. C. Allison, J. Ferrand, H. Chaudhry, J. Emery, A. De Paoli, N. Colon, S. Creed, M. Kaparakis-Liaskos, J. Como, J. K. Dowling, P. A. Johanesen, T. A. Kufer, J. S. Pedersen, A. Mansell, D. J. Philpott, K. D. Elgass, H. E. Abud, U. Nachbur, B. A. Croker, S. L. Masters, R. L. Ferrero
Summary: In mice, NOD1 regulates IL-18 processing in epithelial cells in response to Helicobacter pylori infection via a noncanonical NOD1/caspase-1 pathway. This pathway helps maintain epithelial homeostasis and protects against pre-neoplastic changes induced by the infection.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Immunology
Ioannis Kienes, Sarah Bauer, Clarissa Gottschild, Nora Mirza, Jens Pfannstiel, Martina Schroeder, Thomas Alexander Kufer
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)