Review
Biochemistry & Molecular Biology
Chunfu Zheng
Summary: Members of the MARCH family play important roles in regulating immune system and protein transport in cells, especially in antiviral immune responses. Studies have shown that MARCH affects viral replication by regulating the activity of signaling molecules, impacting host immune defense systems.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Yuko Kozono, Masahiro Kuramochi, Yuji C. Sasaki, Haruo Kozono
Summary: Ubiquitination regulates the lifespan of MHC II complexes on antigen-presenting cells, and disruption of this process can affect the development of CD4+ T cells and regulatory T cells. Overexpression of MARCH I decreases its interaction with LAG-3 and diminishes binding between ubiquitinated MHC II and LAG-3. Single-molecule X-ray imaging revealed that normal MHC II molecules move more rapidly on the cell surface compared to MARCH I-deficient cells or MHC II KR mutants, possibly due to ubiquitination. These findings suggest that ubiquitinated MHC II may not be quickly internalized, but instead present antigens to T cells, leading to significant immunological responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Reema Jain, Kelin Zhao, Julie M. Sheridan, Melanie Heinlein, Fiona Kupresanin, Waruni Abeysekera, Cathrine Hall, James Rickard, Philippe Bouillet, Henning Walczak, Andreas Strasser, John Silke, Daniel H. D. Gray
Summary: The study reveals the crucial role of the linear ubiquitin chain assembly complex in thymic epithelial cell differentiation and survival, with deficiency in LUBAC proteins severely impacting thymic tissue expansion and cell survival, potentially leading to premature thymic atrophy.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Immunology
Jing Song, Warren Anderson, Alex Hu, Kazushige Obata-Ninomiya, Steven F. Ziegler, David J. Rawlings, Jane H. Buckner
Summary: This study utilized gene editing to knock out the CBLB gene in human CD4+ T cells, revealing that CBLB knockout resulted in hyperproliferation and excessive IL-2 production in CD4+ T cells. The knockout cells showed resistance to Treg suppression and were able to overcome Treg inhibition by producing high levels of cytokines, promoting the proliferation and activation of T effector cells.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Namrata Kumar, Arjan F. Theil, Vera Roginskaya, Yasmin Ali, Michael Calderon, Simon C. Watkins, Ryan P. Barnes, Patricia L. Opresko, Alex Pines, Hannes Lans, Wim Vermeulen, Bennett Van Houten
Summary: The repair of UV-induced DNA damage involves nucleotide excision repair proteins, NER proteins DDB2, XPC, and XPA, which play a vital role in 8-oxoguanine repair by coordinating with base excision repair protein OGG1.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Uri Mbonye, Konstantin Leskov, Meenakshi Shukla, Saba Valadkhan, Jonathan Karn
Summary: Understanding the cellular pathways involved in the emergence of HIV from latency is crucial in developing therapeutic approaches for latency reversal. The signaling pathways that regulate the generation of transcriptionally active P-TEFb and reactivation of proviral HIV have been identified, providing potential targets for novel activators of P-TEFb to improve HIV reactivation efficiency.
Article
Multidisciplinary Sciences
Simon Ng, Shuhui Lim, Adrian Chong Nyi Sim, Ruban Mangadu, Ally Lau, Chunsheng Zhang, Sarah Bollinger Martinez, Arun Chandramohan, U-Ming Lim, Samantha Shu Wen Ho, Shih Chieh Chang, Pooja Gopal, Lewis Z. Hong, Adam Schwaid, Aaron Zefrin Fernandis, Andrey Loboda, Cai Li, Uyen Phan, Brian Henry, Anthony W. Partridge
Summary: The study highlights the role of STUB1 in dampening the interferon gamma (IFNγ) response and suggests that inactivating human STUB1 may be a potential strategy to overcome immune checkpoint blockade (ICB) resistance, although it did not show efficacy in mouse tumor models.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Mizuho Kajikawa, Koya Kato, Hayato Takahashi, Seiya Kitajima, Yosuke Kusunoki, Mizuki Haga, Minako Kimura, Yoshihiro Inoue, Kei Miyano, Taisei Kanamoto
Summary: Human herpesvirus 8 (HHV8) uses K3 and K5 proteins to evade the immune system by down-regulating host MHC-I molecules. The cytoplasmic tail of K3 and K5, especially a basic charge cluster near the C-terminus, is important for their protein expression and stability. This study demonstrates that the membrane-distal region of the cytoplasmic tail plays a role in the molecular stability of K3 and K5 by binding to acidic lipids.
MICROBIOLOGY AND IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jiaxin Liu, Yicheng Cheng, Ming Zheng, Bingxiao Yuan, Zimu Wang, Xinying Li, Jie Yin, Mingxiang Ye, Yong Song
Summary: The immune system acts as a fortress against pathogens and tumor cells, but excessive immune responses can lead to harmful effects. Therapeutic antibodies targeting immune checkpoints have made breakthroughs in cancer treatment, but the efficacy of immune checkpoint blockade remains unsatisfactory.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Elena Logli, Elisa Marzuolo, Marco D'Agostino, Libenzio Adrian Conti, Anna Maria Lena, Andrea Diociaiuti, Elena Dellambra, Cristina Has, Valentina Cianfanelli, Giovanna Zambruno, May El Hachem, Alessandra Magenta, Eleonora Candi, Angelo Giuseppe Condorelli
Summary: This study found that fetal keratins in EBS-KLHL24 patients are significantly reduced through proteasome degradation, which may contribute to congenital skin defects. In addition, primary keratinocytes from EBS-KLHL24 patients undergo accelerated clonal conversion and early replicative senescence, suggesting that mutant KLHL24 may contribute to impaired keratinocyte clonogenicity in patients.
HUMAN MOLECULAR GENETICS
(2022)
Article
Immunology
Shivam K. Purohit, Carolyn Samer, Hamish E. G. McWilliam, Renee Traves, Megan Steain, Brian P. McSharry, Paul R. Kinchington, David C. Tscharke, Jose A. Villadangos, Jamie Rossjohn, Allison Abendroth, Barry Slobedman
Summary: This study demonstrates that varicella zoster virus suppresses the expression of antigen presentation molecule MR1, highlighting the intricate temporal relationship between infection and ligand availability. The study also suggests that VZV likely encodes multiple viral genes targeting MR1.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Andrea Di Pietro, Jack Polmear, Lucy Cooper, Timon Damelang, Tabinda Hussain, Lauren Hailes, Kristy O'Donnell, Vibha Udupa, Tian Mi, Simon Preston, Areen Shtewe, Uri Hershberg, Stephen J. Turner, Nicole L. La Gruta, Amy W. Chung, David M. Tarlinton, Christopher D. Scharer, Kim L. Good-Jacobson
Summary: Research reveals that BMI-1 plays a crucial role in chronic viral infections, and targeting BMI-1 can enhance humoral immune responses and accelerate viral clearance. Deficiency of BMI-1 can increase neutralizing and effector function of antibodies, ultimately restoring antibody quality.
Article
Multidisciplinary Sciences
Antonia N. Policheni, Charis E. Teh, Alissa Robbins, Selma Tuzlak, Andreas Strasser, Daniel H. D. Gray
Summary: By investigating compound mutant mice, researchers discovered a cooperative relationship between AIRE and PD-1, the loss of which can lead to spontaneous and lethal autoimmune disease. These findings have important implications for our understanding of how immune checkpoint blockade and defects in central tolerance can synergize to elicit autoimmune diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Haiyin Liu, Kayla R. Wilson, Ashley M. Firth, Christophe Macri, Patrick Schriek, Annabelle B. Blum, Javiera Villar, Samuel Wormald, Mitch Shambrook, Bangyan Xu, Hui Jing Lim, Hamish E. G. McWilliam, Andrew F. Hill, Laura E. Edgington-Mitchell, Irina Caminschi, Mireille H. Lahoud, Elodie Segura, Marco J. Herold, Jose A. Villadangos, Justine D. Mintern
Summary: This study reveals the critical role of ubiquitin-like protein 3 (UBL3) in the trafficking process controlled by MARCH1. UBL3 has wide-ranging immunological consequences and is essential for immune responses.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Charis E. Teh, Simon P. Preston, Alissa K. Robbins, Michael D. Stutz, James Cooney, Michelle P. Clark, Antonia N. Policheni, Cody C. Allison, Liana Mackiewicz, Philip Arandjelovic, Gregor Ebert, Marcel Doerflinger, Tania Tan, Lucille C. Rankin, Peggy P. Teh, Gabrielle T. Belz, Axel Kallies, Andreas Strasser, Marc Pellegrini, Daniel H. D. Gray
Summary: Targeting the immunosuppressive properties of FOXP3(+) regulatory T cells has therapeutic potential for treating autoimmune and inflammatory diseases. This study identifies caspase-8 as a central regulator of T-reg homeostasis, playing a context-specific role during immune responses. Inhibition of caspase-8 leads to accumulation of resistant effector T-regs, while inflammation induces necroptosis of caspase-8-deficient T-regs, enhancing immunity but increasing the risk of lethal inflammation. Additionally, human T-regs exhibit heightened sensitivity to necroptosis compared to conventional T cells.
SCIENCE IMMUNOLOGY
(2022)
Article
Hematology
Rachel Thijssen, Luyi Tian, Mary Ann Anderson, Christoffer Flensburg, Andrew Jarratt, Alexandra L. Garnham, Jafar S. Jabbari, Hongke Peng, Thomas E. Lew, Charis E. Teh, Quentin Gouil, Angela Georgiou, Tania Tan, Tirta M. Djajawi, Constantine S. Tam, John F. Seymour, Piers Blombery, Daniel H. D. Gray, Ian J. Majewski, Matthew E. Ritchie, Andrew W. Roberts, David C. S. Huang
Summary: Researchers used single-cell RNA sequencing to uncover the genetic and epigenetic changes associated with acquired resistance to Venetoclax in chronic lymphocytic leukemia (CLL). They found that these changes involve alterations in the BCL2 family of apoptosis regulators, particularly upregulation of the MCL1 gene and activation of NF-kappa B. MCL1 was identified as a direct transcriptional target of NF-kappa B. These findings highlight the plasticity of CLL cells in evading Venetoclax-induced apoptosis and provide insights for overcoming Venetoclax resistance.
Editorial Material
Cell Biology
Lucille Rankin, Daniel Gray
Summary: This article highlights a recent publication by Whyte et al. that demonstrates the diverse immune outcomes of interleukin (IL)-2 expression in distinct microenvironments. Their definition of context-dependent IL-2 networks opens up possibilities for the development of tissue-specific therapies that harness the powerful immuno-modulatory activity of IL-2.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Christopher Szeto, Pirooz Zareie, Rushika C. Wirasinha, Justin B. Zhang, Andrea T. Nguyen, Alan Riboldi-Tunnicliffe, Nicole L. La Gruta, Stephanie Gras, Stephen R. Daley
Summary: This study describes the contribution of natural covalent bonds between TCR and antigenic peptides in T cell differentiation and activation. The formation of disulfide bonds between TCR and peptide does not require structural rearrangement and can still occur when the initial affinity is low, facilitating T cell activation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Viacheslav Kriachkov, Angelique R. Ormsby, Eric P. Kusnadi, Hamish E. G. McWilliam, Justine D. Mintern, Shanika L. Amarasinghe, Matthew E. Ritchie, Luc Furic, Danny M. Hatters
Summary: Hexanucleotide expansion mutations in C9ORF72 are a common cause of amyotrophic lateral sclerosis. Our study explores the molecular features of translation stalling induced by arginine-rich dipeptide repeats (DPRs) and investigates whether ribosome quality control (RQC) mechanisms regulate translation elongation on sequences encoding DPRs. We found that DPRs lead to stalling in a length-dependent manner and that charged amino acids, such as arginine, lysine, glutamic acid, or aspartic acid, in the DPRs contribute to more pronounced stalling. Furthermore, our findings suggest limited natural regulatory responses to resolve the arginine-rich DPR stalls.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Immunology
Tabinda Hussain, Angela Nguyen, Carmel Daunt, Daniel Thiele, Ee Shan Pang, Jasmine Li, Aidil Zaini, Meredith O'Keeffe, Colby Zaph, Nicola L. Harris, Kylie M. Quinn, Nicole L. La Gruta
Summary: CD8 virtual memory T (TVM) cells, which have undergone partial differentiation in response to cytokines, can increase after helminth infection, leading to improved pathogen clearance in young mice. However, as mice age, TVM cells lose their proliferative capacity and show signs of senescence. In this study, the researchers found that the increase in TVM cells after helminth infection is driven by proliferation of existing TVM cells, rather than differentiation of true naive CD8 T cells. Additionally, TVM cells have the highest proliferation rate compared to other CD8 T cells in response to helminth infection and IL-15. Furthermore, TVM cells from aged mice do not undergo expansion after helminth infection due to intrinsic and extrinsic changes associated with aging.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kerry A. Mullan, Justin B. Zhang, Claerwen M. Jones, Shawn J. R. Goh, Jerico Revote, Patricia T. Illing, Anthony W. Purcell, Nicole L. La Gruta, Chen Li, Nicole A. Mifsud
Summary: This article introduces a web tool called "TCR_Explore" that helps users analyze T cell receptor data from both Sanger sequencing and next generation sequencing platforms. The tool includes automated quality control steps for Sanger sequencing and allows for the generation of publication-ready figures for different sequencing platforms. Users can interact with the web application at https://tcr-explore.erc.monash.edu.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Immunology
Hesham D. D. Abdulla, Raed Alserihi, Christoffer Flensburg, Waruni Abeysekera, Meng-Xiao Luo, Daniel H. D. Gray, Xiaodong Liu, Gordon K. K. Smyth, Warren S. S. Alexander, Ian J. J. Majewski, Matthew P. P. McCormack
Summary: Abdulla et al. demonstrate that the LMO2 transcription factor promotes the development of T-lymphoblastic leukemia by inhibiting thymocyte competition in a transgenic mouse model.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Cell Biology
Lucille C. Rankin, Katherine A. Kaiser, Kenia de los Santos-Alexis, Heekuk Park, Anne-Catrin Uhlemann, Nicholas Arpaia, Daniel H. D. Gray
Summary: Micronutrient deficiency is a leading cause of global diseases. This study reveals that a deficiency in dietary tryptophan (Trp) alters the intestinal microbiome and the immune response, resulting in changes to the Treg cell population. Dietary Trp deficiency leads to the expansion of RORgt+ Treg cells and the loss of Gata3+ Tregs, which can be restored by providing the AhR ligand indole-3-carbinol. These findings emphasize the crucial role of immune-microbiome crosstalk in regulating Treg homeostasis during nutrient deficiency.
Article
Immunology
Caroline L. Ashley, Brian P. McSharry, Hamish E. G. McWilliam, Richard J. Stanton, Ceri A. Fielding, Rommel A. Mathias, David P. Fairlie, James McCluskey, Jose A. Villadangos, Jamie Rossjohn, Allison Abendroth, Barry Slobedman
Summary: This study reveals that human cytomegalovirus (HCMV) inhibits the MR1 pathway and disrupts the MR1:MAIT cell axis through the viral protein gpUS9. The interaction between this virus and MAIT cells in the context of viral infection is not well characterized.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Patrick Schriek, Jose A. Villadangos
Summary: Antigen-presenting cells capture or synthesize antigens and present them on their plasma membrane through major histocompatibility complex (MHC) molecules. Trogocytosis is a mechanism where cells acquire fragments from other cells and incorporate them into their own plasma membrane, including intact antigens and MHC molecules. Trogocytosis expands cellular immunological functions with both beneficial and deleterious consequences.
CURRENT OPINION IN IMMUNOLOGY
(2023)