Article
Biotechnology & Applied Microbiology
Chiara M. M. Cattaneo, Thomas Battaglia, Jos Urbanus, Ziva Moravec, Rhianne Voogd, Rosa de Groot, Koen J. J. Hartemink, John B. A. G. Haanen, Emile E. E. Voest, Ton N. N. Schumacher, Wouter Scheper
Summary: A genetic neoantigen screening system is developed to identify CD4(+) and CD8(+) T cell-recognized neoantigens across patients' complete HLA genotypes.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Miko Valori, Joonas Lehikoinen, Lilja Jansson, Jonna Clancy, Sofie A. Lundgren, Satu Mustjoki, Pentti Tienari
Summary: Somatic mutations in the STAT3 SH2 domain are found in CD8+ cells in multiple sclerosis (MS) patients and controls, with a prevalence of 26%. The mutations are associated with older age and lower neutrophil counts. There is no significant difference in the mutation prevalences between MS patients and controls.
Article
Immunology
Robert Z. Harms, Katie R. Ostlund, Monina Cabrera, Earline Edwards, Victoria B. Smith, Lynette M. Smith, Nora Sarvetnick
Summary: The study found no significant differences in CD8 and double negative MAIT cell frequencies between children with T1D and controls, nor significant associations with T1D-related parameters. However, levels of IL-7, IL-18, 25 (OH) vitamin D, and the ratio of vitamin D binding protein to 25 (OH) vitamin D were associated with MAIT cell frequency. Additionally, previous cytomegalovirus infection was linked to reduced CD8 and DN MAIT cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Leeana D. Peters, Wen- Yeh, Juan M. Arnoletti, Matthew E. Brown, Amanda L. Posgai, Clayton E. Mathews, Todd M. Brusko
Summary: The autoimmune pathogenesis of T1D involves immune cell infiltration into pancreatic islets. CD8(+) T cells play a primary role in killing insulin-producing beta-cells. This study demonstrates the engineering of human T cells to improve the specificity and function of autoreactive CD8(+) T cells, potentially leading to cellular therapeutics for treating autoimmunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Josefine Wadenpohl, Julia Seyfarth, Paul Hehenkamp, Maximilian Hoffmann, Sebastian Kummer, Christina Reinauer, Carsten Doeing, Katharina Foertsch, Ertan Mayatepek, Thomas Meissner, Marc Jacobsen
Summary: This study found significant differences in CD8(+) T cells in children with type 1 diabetes, with potential implications of CD5 expression on immune regulation of CD8(+) T-cell activation.
IMMUNOLOGY AND CELL BIOLOGY
(2021)
Review
Immunology
Connie B. Gilfillan, Michael Hebeisen, Nathalie Rufer, Daniel E. Speiser
Summary: The functional avidity (FA) of cytotoxic CD8 T cells plays a crucial role in their functional capabilities and protection from infection and cancer. The factors influencing FA and its regulation mechanisms are still not fully understood, but recent research suggests that FA may be stable in vivo due to continued signaling modulation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Aenne Harberts, Constantin Schmidt, Joanna Schmid, Daniel Reimers, Friedrich Koch-Nolte, Hans-Willi Mittruecker, Friederike Raczkowski
Summary: IRF4 is essential for the activation and reactivation of CD8(+) memory T cells, but does not affect their overall survival. However, the formation and maintenance of CD8(+) tissue-resident memory T cells appears to depend on IRF4.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Yueyang Sun, Lu Yan, Jiajia Sun, Mingshu Xiao, Wei Lai, Guangqi Song, Li Li, Chunhai Fan, Hao Pei
Summary: Authors have developed a novel platform for identifying T cells using DNA scaffolds to organize pMHCs, allowing detection of low-affinity T cells and enhancing the binding avidity for these cells. This platform shows promise in investigating antigen-specific T cells for immune cell function or immunotherapy applications.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Daisuke Chujo, Akitsu Kawabe, Maya Matsushita, Chiharu Tsutsumi, Fumitaka Haseda, Akihisa Imagawa, Toshiaki Hanafusa, Kohjiro Ueki, Hiroshi Kajio, Kunimasa Yagi, Kazuyuki Tobe, Masayuki Shimoda
Summary: The study revealed significantly upregulated IGRP and ZnT8-specific CD8+ T cell responses in FT1D and AT1D patients, with higher frequencies of IGRP-specific Tc1 cells in the FT1D group. These findings suggest a significant role of IGRP-specific CD8+ T cells in the pathogenesis of FT1D.
CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Tingting Tan, Yufei Xiang, Chao Deng, Chuqing Cao, Zhihui Ren, Gan Huang, Zhiguang Zhou
Summary: This study found that LADA patients have T-cell subset changes resembling both T1D and T2D, suggesting that LADA represents an intermediate type on the diabetes spectrum between T1D and T2D.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
N. Balneger, L. A. M. Cornelissen, M. Wassink, S. J. Moons, T. J. Boltje, Y. E. Bar-Ephraim, K. K. Das, J. N. Sondergaard, C. Bull, G. J. Adema
Summary: The study reveals that sialic acids play a crucial role in regulating the activation and interaction of dendritic cells. Blocking sialic acids enhances the immune activation ability and antigen-induced T cell interactions of dendritic cells. These findings have important implications for understanding the mechanisms of immune responses.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Endocrinology & Metabolism
Sefina Arif, Norkhairin Yusuf, Clara Domingo-Vila, Yuk-Fun Liu, Polly J. Bingley, Mark Peakman
Summary: This study aimed to evaluate T cell phenotypes and metabolic profiles in high-risk individuals who progressed to type 1 diabetes. The results showed a prevalent proinflammatory T cell response in these individuals, which could potentially be used for disease staging and identifying autoantibody-positive individuals.
Review
Cell Biology
Chun-Ting J. Kwong, Claudia Selck, Krisna Tahija, Lachlan J. McAnaney, Dan Le, Thomas W. H. Kay, Helen E. Thomas, Balasubramanian Krishnamurthy
Summary: Despite the promising results in clinical trials, immune interventions for type 1 diabetes mellitus (T1D) have not yet been widely used in clinical practice to achieve insulin independence in patients. The treatment principles for T1D have remained unchanged for almost a century since the discovery of insulin, with a focus on targeting auto-reactive T cells that destroy insulin-producing beta cells. Recent research on CD8(+) T-cell exhaustion suggests potential improvements in markers of T1D, highlighting the need for further study in this area.
IMMUNOLOGY AND CELL BIOLOGY
(2021)
Article
Health Care Sciences & Services
Sara Sokooti, Wendy A. Dam, Tamas Szili-Torok, Jolein Gloerich, Alain J. van Gool, Adrian Post, Martin H. de Borst, Ron T. Gansevoort, Hiddo J. L. Heerspink, Robin P. F. Dullaart, Stephan J. L. Bakker
Summary: Fasting proinsulin levels can serve as a marker of beta-cell dysfunction and predict the development of type 2 diabetes. Hypertension and kidney dysfunction are closely associated with this relationship.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Cell Biology
Stefan Naulaerts, Angeliki Datsi, Daniel M. Borras, Asier Antoranz Martinez, Julie Messiaen, Isaure Vanmeerbeek, Jenny Sprooten, Raquel S. Laureano, Jannes Govaerts, Dena Panovska, Marleen Derweduwe, Michael C. Sabel, Marion Rapp, Weiming Ni, Sean Mackay, Yannick Van Herck, Lendert Gelens, Tom Venken, Sanket More, Oliver Bechter, Gabriele Bergers, Adrian Liston, Steven De Vleeschouwer, Benoit J. Van Den Eynde, Diether Lambrechts, Michiel Verfaillie, Francesca Bosisio, Sabine Tejpar, Jannie Borst, Rudiger V. Sorg, Frederik De Smet, Abhishek D. Garg
Summary: Through multiomics analysis of CD8+ T cell features in multiple patient cohorts and tumor types, we have identified different hypofunctional states of tumor-associated CD8+ T cells, including exhausted CD8+ T cells in supportive tumor niches and hypofunctional CD8+ T cells in nonsupportive niches. These two types of hypofunctional states exhibit distinct characteristics, such as different T cell receptor repertoires and immunopeptidomes. Furthermore, dysfunctional CD4+:CD8+ T cell interactions and a wound healing-like chemokine profile were observed in glioblastoma. Immuno-oncology clinical trials showed that anti-programmed cell death protein 1 (PD-1) immunotherapy exacerbated the tolerogenic disparities in glioblastoma, while dendritic cell (DC) vaccines partially corrected them. Recipients of DC vaccines for glioblastoma demonstrated evidence of antigen-specific immunity.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Juan Huang, Jian Peng, James Alexander Pearson, Georgios Efthimiou, Youjia Hu, Ningwen Tai, Yanpeng Xing, Luyao Zhang, Jianlei Gu, Jianping Jiang, Hongyu Zhao, Zhiguang Zhou, F. Susan Wong, Li Wen
Summary: Deficiency of TLR7 alters B-cell functions, delaying the onset of type 1 diabetes in NOD mice. Additionally, Tlr7(-/-) NOD B cells suppress diabetogenic CD4(+) T-cell responses and protect immunodeficient NOD mice from diabetes.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Immunology
M. Battaglia, J. H. Buckner, M. K. Levings, S. J. Richardson, F. S. Wong, T. I. Tree
Summary: The story of Achilles' heel serves as a metaphor for vulnerability and weakness that may go unnoticed until it causes failure. Various cells and elements have been proposed as potential Achilles' heels for type 1 diabetes, each playing a role in the pathogenesis of the disease.Experts continue to study and present arguments to identify the specific Achilles' heel of T1D.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Joanne Boldison, Terri C. Thayer, Joanne Davies, F. Susan Wong
Summary: Naturally protected NOD mice exhibit unique characteristics in their pancreatic islet morphology and immune infiltrate, with features such as increased frequency of insulin-containing, smaller-sized islets and regulatory T and B cell phenotypes. Despite being diabetes free, they still have significant immune infiltrate, indicating a distinct islet signature and providing new insights into regulatory mechanisms in pancreatic islets.
Review
Endocrinology & Metabolism
Juan Huang, James Alexander Pearson, F. Susan Wong, Li Wen, Zhiguang Zhou
Summary: LADA is an autoimmune disease with features of both type 1 and type 2 diabetes, potentially caused by interactions between islet beta-cells and immune cells. The role of innate immunity in LADA development remains largely unknown, requiring further mechanistic studies to elucidate its contributions. Undertaking these studies will enhance the development of new strategies for disease diagnosis and treatment.
DIABETES-METABOLISM RESEARCH AND REVIEWS
(2022)
Review
Immunology
Stephanie J. Hanna, Danijela Tatovic, Terri C. Thayer, Colin M. Dayan
Summary: In recent years, significant progress has been made in the analysis of individual cells using RNA sequencing techniques, leading to exciting discoveries in the immunology of type 1 diabetes (T1D). Single-cell RNA sequencing has revealed specific gene expression patterns in T1D patients, allowing for predictions of disease development and offering insights into potential immunotherapy targets for T1D.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
James A. Pearson, Heyuan Ding, Changyun Hu, Jian Peng, Brittany Galuppo, F. Susan Wong, Sonia Caprio, Nicola Santoro, Li Wen
Summary: The study suggests that IgM-bound gut microbiota may play a crucial role in the immunopathogenesis of obesity and type 2 diabetes, providing a novel link between IgM and these conditions in both mice and humans.
Review
Endocrinology & Metabolism
Karl Chan, F. Susan Wong, James Alexander Pearson
Summary: Type 2 diabetes mellitus, obesity, and metabolic syndrome are on the rise globally, posing challenges to healthcare systems. Research on circadian rhythms and metabolic diseases suggests that circadian disruption may contribute to metabolic abnormalities. Further investigation into circadian interventions may offer new insights into the management of metabolic diseases.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Medicine, General & Internal
Raffaella Buzzetti, Ernesto Maddaloni, Jason Gaglia, R. David Leslie, F. Susan Wong, Bernhard O. Boehm
Summary: Adult-onset autoimmune diabetes is often misdiagnosed as type 2 diabetes and has a slow progression. Proper care aims to prevent complications and improve quality of life. Choosing the right therapy for this disease is challenging due to its heterogeneity.
NATURE REVIEWS DISEASE PRIMERS
(2022)
Article
Immunology
James A. A. Pearson, Jian Peng, Juan Huang, Xiaoqing Yu, Ningwen Tai, Youjia Hu, Sha Sha, Richard A. A. Flavell, Hongyu Zhao, F. Susan Wong, Li Wen
Summary: The interaction between gut microbiota and host cells can affect susceptibility to Type 1 diabetes through initiating immune responses. NLRP6 protein, a microbe-recognizing inflammasome, deficiency results in the expansion of CD103(+) B cells and protects against Type 1 diabetes. NLRP6-deficient CD103(+) B cells express regulatory markers, secrete higher concentrations of IL-10 and TGFb1 cytokines, and suppress diabetogenic T cell proliferation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Sha Sha, James A. Pearson, Jian Peng, Youjia Hu, Juan Huang, Yanpeng Xing, Luyao Zhang, Ying Zhu, Hongyu Zhao, F. Susan Wong, Li Chen, Li Wen
Summary: TLR9 in B cells modulates T1D susceptibility by changing the frequency and function of IL-10-producing B cells, leading to near-complete protection from diabetes development in NOD mice.
Article
Endocrinology & Metabolism
Terri C. Thayer, Joanne Davies, James A. Pearson, Stephanie J. Hanna, Li Wen, F. Susan Wong
Summary: Our results suggest that a loss of NOD-LNSC MHC-independent suppressive mechanisms may contribute to diabetes development. In contrast, non-MHC-matched, control C57BL/6 mouse LNSC suppressed T-cell receptor engagement by anti-CD3/CD28 via MHC-independent mechanisms, modifying antigen sensitivity and effector function.