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
Cell Biology
Sarah L. Snelgrove, Olivia Susanto, Louisa Yeung, Pamela Hall, M. Ursula Norman, Alexandra J. Corbett, A. Richard Kitching, Michael J. Hickey
Summary: This study developed a flow cytometry strategy to characterize the phenotype and response of DN T cells in the kidney. The experiments revealed that DN T cells are primarily located within the renal parenchyma and have an effector memory phenotype. Following renal ischemia-reperfusion injury, the number of DN T cells significantly increases after 72 hours, partly due to recruitment from the circulation. The observation that DN T cells can upregulate CD8 in vivo has important implications for future studies.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Cell Biology
Anouk von Borstel, Thi H. O. Nguyen, Louise C. Rowntree, Thomas M. Ashhurst, Lilith F. Allen, Lauren J. Howson, Natasha E. Holmes, Olivia C. Smibert, Jason A. Trubiano, Claire L. Gordon, Allen C. Cheng, Stephen J. Kent, Jamie Rossjohn, Katherine Kedzierska, Martin S. Davey
Summary: SARS-CoV-2 infection can cause severe COVID-19 in some individuals. The immune system, particularly effector gamma delta T cells, plays a role in the defense against SARS-CoV-2. Our study shows an association between effector populations of gamma delta T cells and acute COVID-19 in unvaccinated individuals.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Immunology
Gwennaelle C. Monnot, Marcin Wegrecki, Tan-Yun Cheng, Yi-Ling Chen, Brigitte N. Sallee, Reka Chakravarthy, Ioanna Maria Karantza, Shin Yi Tin, Alexandra E. Khaleel, Isha Monga, Laura N. Uwakwe, Alice Tillman, Bin Cheng, Soundos Youssef, Soo Weei Ng, Adam Shahine, Javier A. Garcia-Vilas, Anne-Catrin Uhlemann, Lindsey A. Bordone, Arnold Han, Christine H. Rohde, Graham Ogg, D. Branch Moody, Jamie Rossjohn, Annemieke de Jong
Summary: CD1a presents a range of self-lipid antigens found within the skin. The study identifies CD1a-dependent T cell responses to bacterial membrane phospholipids and suggests a link between PG-based lipid-activated T cells and atopic dermatitis pathogenesis. The expansion of CD4(+) CD1a-(lysyl)PG tetramer(+) T cells in patients with atopic dermatitis supports the involvement of bacteria-associated lipids in the development of this condition.
Article
Immunology
Maya M. L. Poon, Daniel P. P. Caron, Zicheng Wang, Steven B. B. Wells, David Chen, Wenzhao Meng, Peter A. A. Szabo, Nora Lam, Masaru Kubota, Rei Matsumoto, Adeeb Rahman, Eline T. Luning T. Prak, Yufeng Shen, Peter A. A. Sims, Donna L. L. Farber
Summary: This study examines the differences in phenotypic, transcriptomic, clonal, and functional characteristics between tissue-resident T cells and circulating T cells in various barrier tissue sites in humans. The findings suggest that circulating T cells are more disseminated and differentiated, while tissue-resident T cells exhibit tissue-specific adaptation and clonal segregation, highlighting the importance of tissue targeting strategies for promoting barrier immunity.
Review
Immunology
Peter A. Szabo
Summary: Tissue-resident memory T cells (TRM) are a specialized localized immune memory layer in the human body, present in almost every organ. They exhibit remarkable heterogeneity in form and function, shaped by various site-specific influences. This review discusses the surface phenotypes, transcriptional programming, and tissue-specific adaptations of TRM, as well as the mechanisms and models for TRM generation. Understanding the differentiation, function, and maintenance of different subpopulations within the TRM lineage could unlock the full potential of TRM in promoting localized tissue immunity throughout the body.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Cell Biology
Timothy Patton, Zhe Zhao, Xin Yi Lim, Eleanor Eddy, Huimeng Wang, Adam G. Nelson, Bronte Ennis, Sidonia B. G. Eckle, Michael N. T. Souter, Troi J. Pediongco, Hui-Fern Koay, Jian-Guo Zhang, Tirta M. Djajawi, Cynthia Louis, Najoua Lalaoui, Nicolas Jacquelot, Andrew M. Lew, Daniel G. Pellicci, James McCluskey, Yifan Zhan, Zhenjun Chen, Kate E. Lawlor, Alexandra J. Corbett
Summary: Cell death mechanisms in T lymphocytes vary depending on their developmental stage, cell subset, and activation status. However, the cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are not well understood. In this study, it was found that MAIT cells express high levels of key necroptotic machinery, RIPK3 and MLKL proteins. Surprisingly, the loss of RIPK3, but not MLKL or caspase-8, specifically increased the abundance of MAIT cells in various organs, indicating a cell-intrinsic regulation of MAIT cell accumulation by RIPK3 signaling.
CELL DEATH & DISEASE
(2023)
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)
Article
Allergy
Nicole A. A. Mifsud, Patricia T. T. Illing, Rebecca Ho, Johanna E. E. Tuomisto, Heidi Fettke, Kerry A. A. Mullan, James McCluskey, Jamie Rossjohn, Julian Vivian, Rangsima Reantragoon, Anthony W. W. Purcell
Summary: Allopurinol is a drug used in the treatment of gout but can cause severe and life-threatening hypersensitivity reactions. People carrying the HLA-B*58:01 allotype are at higher risk. The drug metabolite oxypurinol is responsible for T cell-mediated immunopathology, and the TCR repertoire usage of reactive T cells in ALP-induced hypersensitivity reactions has been limitedly studied. This research shows that oxypurinol drives CD8(+) T cell responses and that drug-exposed memory T cells exhibit a proinflammatory immunophenotype. The study also supports the concept of pharmacological interaction with immune receptors and highlights oligoclonal and private clonotypic profiles of OXP-induced TCRs.
Review
Immunology
Wael Awad, Lisa Ciacchi, James McCluskey, David P. Fairlie, Jamie Rossjohn
Summary: Metabolite-based T-cell immunity plays a crucial role in antimicrobial immunity, autoimmunity, and cancer. This review summarizes the impact of metabolite recognition and modulation on mucosal-associated invariant T cells (MAIT), providing a framework for understanding the molecular correlates of MAIT T cell receptor (TCR)-MR1 recognition.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Oncology
Edith Borcoman, Ana Lalanne, Jean-Pierre Delord, Philippe A. Cassier, Frederic Rolland, Sebastien Salasi, Jean-Marc Limacher, Olivier Capitain, Olivier Lantz, Christina Ekwegbara, Emmanuelle Jeannot, Joanna Cyrta, Carine Tran-Perennou, Zahra Castel-Ajgal, Gregoire Marret, Eliane Piaggio, Maud Brandely, Annette Tavernaro, Hakim Makhloufi, Kaidre Bendjama, Christophe Le Tourneau
Summary: This study evaluated the use of the TG4001 viral immunotherapeutic vaccine in combination with avelumab in HPV16+ cancer patients, and found that it was safe and effective in treating this type of cancer.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Robert C. Kuiack, Stephen W. Tuffs, Karine Dufresne, Robert Flick, John K. McCormick, Martin J. McGavin
Summary: In Staphylococcus aureus, the fadXDEBA locus is responsible for metabolizing fatty acids, while the function of this locus remains unknown. Previous studies suggested that the fatty acid kinase FakA pathway is the only option for S. aureus to metabolize exogenous saturated fatty acids. However, in the USA300 strain of S. aureus, the fadX::lux reporter was repressed by glucose and induced by palmitic acid but not stearic acid. Additionally, deletion of fakA resulted in significantly elevated basal expression and enhanced response to both fatty acids. These findings suggest that the FakA pathway is the preferred pathway for metabolizing exogenous fatty acids, while the fad locus is critical for metabolizing palmitic acid.
MOLECULAR MICROBIOLOGY
(2023)
Article
Immunology
Adam G. Nelson, Huimeng Wang, Phoebe M. Dewar, Eleanor M. Eddy, Songyi Li, Xin Yi Lim, Timothy Patton, Yuchen Zhou, Troi J. Pediongco, Lucy J. Meehan, Bronwyn S. Meehan, Jeffrey Y. W. Mak, David P. Fairlie, Andrew W. Stent, Lars Kjer-Nielsen, James Mccluskey, Sidonia B. G. Eckle, Alexandra J. Corbett, Michael N. T. Souter, Zhenjun Chen
Summary: This study outlines three methods to increase the abundance of mucosal-associated invariant T (MAIT) cells in C57BL/6 mice. The administration of synthetic 5-amino-6-D-ribitylaminouracil (5-A-RU) in combination with inflammatory stimuli has been shown to significantly increase the frequency and absolute numbers of MAIT cells in mice. These increased MAIT cells are functional and can provide protection against lethal infections.
FRONTIERS IN IMMUNOLOGY
(2023)