Review
Endocrinology & Metabolism
Christine Bender, Sakthi Rajendran, Matthias G. von Herrath
Summary: The establishment of the nPOD network has provided unprecedented insight into the pathology of human type 1 diabetes, revealing the presence of autoreactive CD8 T cells even in healthy individuals and the potential role of beta-cell-intrinsic events in attracting them to islets. Additionally, signs of beta-cell dysfunction, potentially related to stress, such as over-expression of certain cytokines, are being discovered. This review focuses on cytokines and autoreactive CD8 T cells in the pathogenesis of human type 1 diabetes.
FRONTIERS IN ENDOCRINOLOGY
(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
Immunology
Tina De Bruyn Carlier, Fariza Mishaal Saiema Badloe, Johannes Ring, Jan Gutermuth, Inge Kortekaas Krohn
Summary: Atopic dermatitis is a chronic inflammatory skin disease that develops in early childhood and is associated with food allergy, with immune reactions potentially leading to autoimmune processes. The exact mechanisms of IgE-mediated autoimmunity and self-reactive T cells in the pathophysiology of AD are still unclear.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Daniel A. Michelson, Koji Hase, Tsuneyasu Kaisho, Christophe Benoist, Diane Mathis
Summary: Medullary thymic epithelial cells (mTECs) ectopically express thousands of peripheral-tissue antigens (PTAs), which drive deletion or phenotypic diversion of self-reactive immature T cells during thymic differentiation. Lineage-defining transcription factors (TFs) for distinct cell types are present in different mTEC subtypes, and these factors are essential for the accumulation of mimetic cells and the expression of PTAs, contributing to self-tolerance.
Article
Immunology
Georges Abboud, Seung-Chu Choi, Xiaojuan Zhang, Yuk Pheel Park, Nathalie Kanda, Leilani Zeumer-Spataro, Morgan Terrell, Xiangyu Teng, Kirsten Nundel, Mark J. Shlomchik, Laurenc Morel
Summary: The activation of lymphocytes in lupus is associated with increased cellular metabolism, particularly glycolysis. Inhibiting glycolysis reversed the expansion of specific T and B cells and reduced autoantibody production in lupus-prone mice. However, foreign antigens were not affected, suggesting a unique sensitivity of autoreactive B and CD4+ T cells to glycolysis.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Marcin Wegrecki, Tonatiuh A. Ocampo, Sachith D. Gunasinghe, Anouk von Borstel, Shin Yi Tin, Josephine F. Reijneveld, Thinh-Phat Cao, Benjamin S. Gully, Jerome Le Nours, D. Branch Moody, Ildiko Van Rhijn, Jamie Rossjohn
Summary: In this study, the authors reveal a novel geometrically alternate sideways mode of recognition of the antigen-presenting molecule CD1a by a gamma delta T cell receptor. The gamma delta TCR binds CD1a in a lipid-independent manner and induces clustering of TCRs and T cell signaling.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Patricia Sole, Pere Santamaria
Summary: Systemic delivery of pMHC class II-based nanomedicines can re-program CD4+ T cells into TR1-like cells, which suppress organ-specific autoimmunity effectively. The true identity and direct precursors of TR1-like cells remain unclear, and further transcriptional and epigenetic characterization of homogeneous pools of these cells is needed to unravel this mystery.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Sihan Wu, Xuan Zhang, Cuiping Hu, Yajie Zhong, Jun Chen, Wai Po Chong
Summary: This study found that the activation of CD8(+) T cells significantly suppressed the cytokine production of Th1 and Th17 cells, and this treatment had a therapeutic effect in experimental autoimmune uveitis. Additionally, IFN-gamma(+) CD8(+) T cells were recruited more efficiently into lymphoid organs during the disease-priming phase, and this recruitment depended on the CXCR3 receptor.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Quanri Zhang, Weiwei Liu, Han Wang, Hao Zhou, Katarzyna Bulek, Xing Chen, Cun-Jin Zhang, Junjie Zhao, Renliang Zhang, Caini Liu, Zizhen Kang, Robert A. Bermel, George Dubyak, Derek W. Abbott, Tsan Sam Xiao, Laura E. Nagy, Xiaoxia Li
Summary: The C-type lectin receptor Mincle plays a crucial role in promoting central nervous system inflammation by sensing danger signals on TH17 cells.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Murilo Delgobo, Margarete Heinrichs, Nils Hapke, DiyaaElDin Ashour, Marc Appel, Mugdha Srivastava, Tobias Heckel, Ioakim Spyridopoulos, Ulrich Hofmann, Stefan Frantz, Gustavo Campos Ramos
Summary: The cardiovascular and immune systems undergo significant changes with aging, and an accumulation of CD4(+) T cells in elderly individuals may contribute to myocardial aging and heart disease progression. By studying young mice with expanded CD4(+) T cell compartments, researchers found that these cells can differentiate and impact the heart, suggesting a link between immunological senescence and age-related cardiac deterioration.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Shreya Mathur, Jo-Chiao Wang, Corey R. Seehus, Florence Poirier, Theo Crosson, Yu-Chen Hsieh, Benjamin Doyle, Seungkyu Lee, Clifford J. Woolf, Simmie L. Foster, Sebastien Talbot
Summary: Nociceptors, high-threshold primary sensory neurons triggering pain, were found to play a key role in modulating adaptive immune responses in allergic inflammation models, particularly in B cell antibody class switching to IgE. Their interaction with immune cells not only affects innate immunity, but also influences IgE production in allergic inflammation.
Article
Chemistry, Multidisciplinary
Arbel Artzy-Schnirman, Enas Abu-Shah, Rona Chandrawati, Efrat Altman, Norkhairin Yusuf, Shih-Ting Wang, Jose Ramos, Catherine S. Hansel, Maya Haus-Cohen, Rony Dahan, Sefina Arif, Michael L. Dustin, Mark Peakman, Yoram Reiter, Molly M. Stevens
Summary: The study develops a unique artificial antigen-presenting cell system that can detect and target autoreactive T-cell populations, providing a promising tool for preventing autoimmune diseases.
Review
Immunology
Ana Pires, Stephanie Burnell, Awen Gallimore
Summary: This review examines the relationship between immune cells and the extracellular matrix in the context of cancer immunotherapy, and discusses how this interaction influences tumor progression.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Hisato Iriki, Hayato Takahashi, Naoko Wada, Hisashi Nomura, Miho Mukai, Aki Kamata, Hiromi Ito, Jun Yamagami, Takeshi Matsui, Yutaka Kurebayashi, Setsuko Mise-Omata, Hiroshi Nishimasu, Osamu Nureki, Akihiko Yoshimura, Shohei Hori, Masayuki Amagai
Summary: The study analyzed peripheral tolerance using the Dsg3 antigen and found that Treg-mediated peripheral deletion of autoreactive T cells is a key mechanism to avoid undesired autoimmunity, which is dependent on the OX40 signaling pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Nai-Wen Fan, Qiurong Zhu, Shudan Wang, Gustavo Ortiz, Rachel M. Huckfeldt, Yihe Chen
Summary: Chronic uveitis is a group of clinical entities characterized by sustained and recurrent intraocular inflammation that is believed to be driven by autoimmune responses. In this study, a murine model of chronic autoimmune uveitis was used to investigate the cellular mechanisms underlying chronic intraocular inflammation. The results showed the presence of unique long-lived CD4(+) memory T cells in the retina and secondary lymphoid organs after 3 months of inducing autoimmune uveitis. These memory T cells exhibited antigen-specific proliferation and activation in response to retinal peptide stimulation. Furthermore, they were found to be capable of effectively trafficking to the retina and causing retinal damage. The findings suggest that memory T cells may be a potential therapeutic target for treating chronic uveitis.
Article
Immunology
A. Flores-Langarica, K. Mueller Luda, E. K. Persson, C. N. Cook, S. Bobat, J. L. Marshall, M. W. Dahlgren, K. Hagerbrand, K. M. Toellner, M. D. Goodall, D. R. Withers, I. R. Henderson, B. Johansson Lindbom, A. F. Cunningham, W. W. Agace
MUCOSAL IMMUNOLOGY
(2018)
Article
Cell Biology
Kai-Michael Toellner, Daniel M-Y Sze, Yang Zhang
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2018)
Article
Immunology
Yang Zhang, Laura Tech, Laura A. George, Andreas Acs, Russell E. Durrett, Henry Hess, Lucy S. K. Walker, David M. Tarlinton, Anne L. Fletcher, Anja Erika Hauser, Kai-Michael Toellner
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Microbiology
Anna E. Schager, C. Coral Dominguez-Medina, Francesca Necchi, Francesca Micoli, Yun Shan Goh, Margaret Goodall, Adriana Flores-Langarica, Saeeda Bobat, Charlotte N. L. Cook, Melissa Arcuri, Arianna Marini, Lloyd D. W. King, Faye C. Morris, Graham Anderson, Kai-Michael Toellner, Ian R. Henderson, Constantino Lopez-Macias, Calman A. MacLennan, Adam F. Cunningham
Article
Multidisciplinary Sciences
Matthew G. Darby, Alisha Chetty, Dunja Mrjden, Marion Rolot, Katherine Smith, Claire Mackowiak, Delphine Sedda, Donald Nyangahu, Heather Jaspan, Kai-Michael Toellner, Ari Waisman, Valerie Quesniaux, Bernhard Ryffel, Adam F. Cunningham, Benjamin G. Dewals, Frank Brombacher, William G. C. Horsnell
Article
Immunology
Jonathan A. Roco, Luka Mesin, Sebastian C. Binder, Christian Nefzger, Paula Gonzalez-Figueroa, Pablo F. Canete, Julia Ellyard, Qian Shen, Philippe A. Robert, Jean Cappello, Harpreet Vohra, Yang Zhang, Carla R. Nowosad, Arien Schiepers, Lynn M. Corcoran, Kai-Michael Toellner, Jose M. Polo, Michael Meyer-Hermann, Gabriel D. Victora, Carola G. Vinuesa
Article
Immunology
Vitalijs Ovcinnikovs, Ellen M. Ross, Lina Petersone, Natalie M. Edner, Frank Heuts, Elisavet Ntavli, Alexandros Kogimtzis, Alan Kennedy, Chun Jing Wang, Clare L. Bennett, David M. Sansom, Lucy S. K. Walker
SCIENCE IMMUNOLOGY
(2019)
Article
Immunology
Natalie M. Edner, Frank Heuts, Niclas Thomas, Chun Jing Wang, Lina Petersone, Rupert Kenefeck, Alexandros Kogimtzis, Vitalijs Ovcinnikovs, Ellen M. Ross, Elisavet Ntavli, Yassin Elfaki, Martin Eichmann, Roman Baptista, Philip Ambery, Lutz Jermutus, Mark Peakman, Miranda Rosenthal, Lucy S. K. Walker
Review
Biotechnology & Applied Microbiology
Natalie M. Edner, Gianluca Carlesso, James S. Rush, Lucy S. K. Walker
NATURE REVIEWS DRUG DISCOVERY
(2020)
Correction
Biotechnology & Applied Microbiology
Natalie M. Edner, Gianluca Carlesso, James S. Rush, Lucy S. K. Walker
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Multidisciplinary Sciences
Juan Carlos Yam-Puc, Lingling Zhang, Raul A. Maqueda-Alfaro, Laura Garcia-Ibanez, Yang Zhang, Jessica Davies, Yotis A. Senis, Michael Snaith, Kai-Michael Toellner
Summary: The study found that BCR signaling not only influences B cell selection and proliferation, but also can trigger cell apoptosis and suppress affinity maturation in the long term.
Editorial Material
Immunology
Yang Zhang, Kai-Michael Toellner
Summary: Liu et al. demonstrate in this study that T cell-independent germinal centers can generate long-lived memory cells and plasma cell output, which may explain the long-term protection provided by polysaccharide antigens.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Review
Immunology
Di Yu, Lucy S. K. Walker, Zheng Liu, Michelle A. Linterman, Zhanguo Li
Summary: Yu et al. review the crucial roles of follicular helper T cells in humoral immunity, including sustaining germinal center B cell responses, regulating antibody affinity maturation and memory formation, and mediating pathogenic autoimmune responses. Understanding the regulation of follicular helper T cell generation and function is important for disease prevention and treatment, as well as vaccine development and enhancement.
Article
Immunology
Lucy S. K. Walker
Summary: This article discusses the increased frequency of T cells bearing features of follicular helper T cells in individuals with autoimmunity, and explores potential explanations for this phenomenon. The regulation of T-FH cell differentiation by pathways such as CTLA4 and IL-2, as well as regulatory T cells, is considered, highlighting their crucial role in autoimmune diseases. The potential role of infection in triggering T-FH cell differentiation and autoimmune disease development is also discussed. Overall, the author postulates that alterations in pathways that regulate autoimmunity are coupled to alterations in T-FH cell homeostasis, suggesting that this population may serve as a core sentinel of dysregulated immunity.
NATURE REVIEWS IMMUNOLOGY
(2022)
Article
Cell Biology
Emma Jennings, Thomas A. E. Elliot, Natasha Thawait, Shivani Kanabar, Juan Carlos Yam-Puc, Masahiro Ono, Kai-Michael Toellner, David C. Wraith, Graham Anderson, David Bending