Review
Immunology
Yisi Lu, Joe Craft
Summary: T follicular regulatory cells are a unique subset of regulatory T cells that migrate to B cell follicles and germinal centers to maintain immune homeostasis. They use specific transcription factors to regulate immune responses, promoting humoral immunity and memory following viral infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Chun-Shu Wong, Clarisa M. Buckner, Silvia Lucena Lage, Luxin Pei, Felipe L. Assis, Eric W. Dahlstrom, Sarah L. Anzick, Kimmo Virtaneva, Adam Rupert, Jeremy L. Davis, Ting Zhou, Elizabeth Laidlaw, Maura Manion, Frances Galindo, Megan Anderson, Catherine A. Seamon, Michael C. Sneller, Andrea Lisco, Claire Deleage, Stefania Pittaluga, Susan Moir, Irini Sereti
Summary: Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality, and lasting immune dysfunction. In severely lymphopenic HIV+ patients, early events of immune recovery have not been fully characterized. Post-ART, there were signs of immune reconstitution with an increase in LN germinal center cells, although limited in functionality.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Fang Ke, Zachary L. Benet, Mitra P. Maz, Jianhua Liu, Alexander L. Dent, Joanne Michelle Kahlenberg, Irina L. Grigorova, Tomohiro Kurosaki
Summary: This study found that nuclear proteins contain antigens specific to Tfr. Targeting these proteins to antigen-specific B cells in mice leads to rapid accumulation of immunosuppressive Tfr. Tfr exerts predominant inhibition on GC B cells acquiring nuclear proteins, suggesting the important role of direct cognate Tfr-GC B cells interactions in controlling effector B cell response.
Article
Cardiac & Cardiovascular Systems
Fabienne Burger, Kapka Miteva, Daniela Baptista, Aline Roth, Rodrigo A. Fraga-Silva, Catherine Martel, Nikolaos Stergiopulos, Francois Mach, Karim J. Brandt
Summary: The study shows that follicular regulatory helper T cells (T-FR) can control regulatory B cell (B-REG) populations in mice models on a high-cholesterol diet, leading to the suppression of proatherogenic processes. This suggests that T-FR cells may have atheroprotective effects by modulating immune processes related to atherosclerosis.
CARDIOVASCULAR RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Jian Lu, Jing Wu, Xueli Xia, Huiyong Peng, Shengjun Wang
Summary: RA is a chronic autoimmune disease characterized by joint and systemic inflammation, with Tfh cells playing a crucial role in the pathogenesis of the disease and affecting disease activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Immunology
Filipa Ribeiro, Esperanza Perucha, Luis Graca
Summary: This article reviews the development and biology of T follicular cell subsets, with a special emphasis on the metabolic regulation of Tfh cells, contributing to a better understanding of GC responses.
IMMUNOLOGY LETTERS
(2022)
Article
Immunology
Rui-Ting Liu, Wei Li, Dong Guo, Chun-Lin Yang, Jie Ding, Jian-Xin Xu, Rui-Sheng Duan
Summary: The study found that NK cells in patients with myasthenia gravis have abnormal immune-regulation on CD4(+) T cells and Tfh cells, which may contribute to the immune-pathological mechanism of MG.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Immunology
Nengqi Lin, Wei Yin, Heather Miller, Maria G. Byazrova, Andres A. Herrada, Kamel Benlagha, Pamela Lee, Fei Guan, Jiahui Lei, Quan Gong, Youqing Yan, Alexander Filatov, Chaohong Liu
Summary: Hepatitis B has become a major health threat worldwide, particularly in developing countries and regions. Infection with hepatitis B virus significantly increases the risk of liver diseases such as cirrhosis and cancer. The immune response against hepatitis B is mainly regulated by CD8+ T cells, which play a key role in fighting viral infections, while regulatory T cells prevent excessive immune response. Additionally, follicular T helper cells have a critical role in B-cell activation, proliferation, differentiation, and the formation of germinal centers. The development of hepatitis B virus is generally associated with immune system disorders or dysfunctions. This review focuses on the important functions and biological processes of regulatory T cells and follicular T helper cells during HBV infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Etienne Masle-Farquhar, Yogesh Jeelall, Jacqueline White, Julia Bier, Elissa K. Deenick, Robert Brink, Keisuke Horikawa, Christopher Carl Goodnow
Summary: This study investigated the effects of CARD11 gene mutations on B and T lymphocytes in a disease associated with B cell expansion and T cell anergy, as well as in certain lymphomas. The results showed that the mutations increased the activation and proliferation of B and T lymphocytes following antigen receptor stimulation, and led to increased expression of checkpoint molecules on T cells. This study reveals CARD11 as an important positive regulator of T cells and highlights the cell-intrinsic effects of CARD11 mutations on T cell malignancies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Kalliopi Ioannidou, Daba-Rokhya Ndiaye, Alessandra Noto, Craig Fenwick, Sotirios P. Fortis, Giuseppe Pantaleo, Constantinos Petrovas, Laurence de Leval
Summary: This study utilized a quantitative multiplexed immunofluorescence approach to comprehensively characterize Tfh cells in human tonsils and lymph nodes. Different subsets of Tfh cells were identified at tissue level based on differential expression of surface receptors and nuclear factors. Moreover, significant differences in Tfh cell profile signatures between health and disease were revealed.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Jingjing Qi, Chang Liu, Ziran Bai, Xia Li, Genhong Yao
Summary: Tfh cells and Tfr cells play crucial roles in the pathogenesis of autoimmune diseases, regulating B cell differentiation and antibody production by expressing specific surface markers and cytokines. Understanding the phenotype, differentiation, and function of these cells may provide insight into potential therapies targeting the balance of Tfh and Tfr cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Matthew T. T. Ollerton, Joy M. M. Folkvord, Andriana La Mantia, David A. A. Parry, Amie L. L. Meditz, Martin D. D. McCarter, Richard T. D'Aquila, Elizabeth Connick
Summary: Follicular helper CD4(+) T cells (TFH) are major sites of HIV replication, but follicular regulatory CD4(+) T cells (TFR) limit HIV replication by suppressing TFH through IL-2 restriction. TFR reduce TFH viability and HIV infected TFH, and IL-2 enhances TFH viability but decreases HIV replication in the presence of TFR.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Margaret H. O'Connor, Roshell Muir, Marita Chakhtoura, Michael Fang, Eirini Moysi, Susan Moir, Alison J. Carey, Alyssa Terk, Carmen N. Nichols, Talibah Metcalf, Constantinos Petrovas, Mark J. Cameron, Virginie Tardif, Elias K. Haddad
Summary: Researchers report a new population of Innate Lymphoid Cells in human tonsils and lymph nodes that inhibit the functional interaction of follicular helper T cells and germinal center B cells. They show that this cell population is expanded under chronic HIV infection, resulting in decreased antibody production, suggesting a potential role for these cells in diseases with dysregulated immune responses.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Bradley Salvatore, Rachel S. Resop, Brent R. Gordon, Marta Epeldegui, Otoniel Martinez-Maza, Begona Comin-Anduix, Alex Lam, Ting-Ting Wu, Christel H. Uittenbogaart
Summary: Humoral immune response plays a crucial role in combating pathogens by producing specific antibodies. T follicular helper (TFH) cells contribute to both B-cell antibody production and HIV persistence. T follicular regulatory (TFR) cells, which suppress TFH cell function, exhibit similar surface markers. The increase in TFH cells observed in HIV infection may partially be due to an increase in TFR cells. Using multicolor flow cytometry, we identified peripheral blood TFH (pTFH) and peripheral blood TFR (pTFR) cells and found that the frequency of pTFH cells was higher in HIV-infected individuals. Additionally, pTFH cells expressed lower levels of CCR5, a key factor in HIV persistence. The constitutive expression of CCR5 in TFR cells indicates their potential contribution to HIV persistence.
Article
Engineering, Biomedical
Mai N. Vu, Hannah G. Kelly, Hyon-Xhi Tan, Jennifer A. Juno, Robyn Esterbauer, Thomas P. Davis, Nghia P. Truong, Adam K. Wheatley, Stephen J. Kent
Summary: This study presents a facile method to produce lipid nanoparticle subunit vaccines that exhibit high immunogenicity and provide protection against influenza virus. The vaccines showed increased serum antibody titers and superior protection against highly pathogenic viruses, along with enhanced B cell and follicular helper T cell responses. This work facilitates the rational design and rapid production of next generation nanoparticle subunit vaccines.
ADVANCED HEALTHCARE MATERIALS
(2021)
Correction
Oncology
Yichao Hua, Gerlanda Vella, Florian Rambow, Elizabeth Allen, Asier Antoranz Martinez, Marie Duhamel, Akira Takeda, Sirpa Jalkanen, Steffie Junius, Ann Smeets, David Nittner, Stefanie Dimmeler, Thomas Hehlgans, Adrian Liston, Francesca Maria Bosisio, Giuseppe Floris, Damya Laoui, Maija Hollmen, Diether Lambrechts, Pascal Merchiers, Jean-Christophe Marine, Susan Schlenner, Gabriele Bergers
Review
Allergy
Mathijs Willemsen, Frederik Staels, Margaux Gerbaux, Julika Neumann, Rik Schrijvers, Isabelle Meyts, Stephanie Humblet-Baron, Adrian Liston
Summary: Inborn errors of immunity are a group of diverse monogenic immunologic disorders caused by mutations in genes involved in the immune system. Some mutations occur in genes with restricted expression and/or function in immune cells, while others affect genes that are ubiquitously expressed. These genetic defects can lead to deficiencies in DNA replication, repair, or damage response factors, resulting in immunodeficiency. Understanding the mechanistic insights of these DNA replication-associated inborn errors of immunity is crucial for comprehending the observed heterogeneity in clinical manifestations and immunologic defects.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Editorial Material
Immunology
Adrian Liston, Lidia Yshii
Summary: Aging is often associated with cognitive decline caused by brain degeneration. Recent research provides further evidence of the connection between CD8(+) T cells, interferon-gamma production in the brain, and neurodegeneration.
Article
Multidisciplinary Sciences
Amelie Bonaud, Laetitia Gargowitsch, Simon M. Gilbert, Elanchezhian Rajan, Pablo Canales-Herrerias, Daniel Stockholm, Nabila F. Rahman, Mark O. Collins, Hakan Taskiran, Danika L. Hill, Andres Alloatti, Nagham Alouche, Stephanie Balor, Vanessa Soldan, Daniel Gillet, Julien Barbier, Francoise Bachelerie, Kenneth G. C. Smith, Julia Jellusova, Pierre Bruhns, Sebastian Amigorena, Karl Balabanian, Michelle A. Linterman, Andrew A. Peden, Marion Espeli
Summary: We identified SNARE Sec22b as a critical regulator of plasma cell maintenance and function. In the absence of Sec22b, plasma cells were hardly detectable and serum antibody titers were dramatically reduced, leading to a failure in mounting a protective immune response. Mechanistically, Sec22b contributes to efficient antibody secretion and is involved in regulating plasma cell transcriptional identity, as well as the morphology of the endoplasmic reticulum and mitochondria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
William S. Foster, Joseph Newman, Nazia Thakur, Alexandra J. Spencer, Sophie Davies, Danielle Woods, Leila Godfrey, Sarah H. Ross, Hayley J. Sharpe, Arianne C. Richard, Dalan Bailey, Teresa Lambe, Michelle A. Linterman
Summary: Effective vaccines have reduced the impact of SARS-CoV-2 infection, but the elderly are still at high risk. Understanding vaccine-induced immunity and how it changes with age is important for future vaccine development. CD8(+) T cells play a crucial role in killing infected cells, and vaccines that stimulate both CD8(+) T cell responses and humoral immunity provide additional protection, especially in older individuals. The study shows that the ChAdOx1 nCoV-19 vaccine generates a good CD8(+) T-cell response in older mice, but age-related differences in T-cell characteristics are observed.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Article
Immunology
Margaux Gerbaux, Evelyne Roos, Mathijs Willemsen, Frederik Staels, Julika Neumann, Leoni Bucken, Jeason Haughton, Lidia Yshii, James Dooley, Susan Schlenner, Stephanie Humblet-Baron, Adrian Liston
Summary: This study compares the efficacy of three main therapeutic candidates (rapamycin, nondepleting anti-CD4 antibody, and CTLA4-Ig) in treating FOXP3-deficient mice, and suggests that CTLA4-Ig may be a superior therapeutic option for FOXP3-deficient patients.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Review
Multidisciplinary Sciences
Carola G. Vinuesa, Amalie Grenov, George Kassiotis
Summary: While all multicellular organisms possess germ line-encoded innate receptors, vertebrates have also developed adaptive immunity based on somatically generated antigen receptors. These two systems are interconnected, with innate immunity playing a crucial role in inducing adaptive antiviral immunity. This review focuses on how inborn errors of innate immunity can lead to B cell autoimmunity, with increased nucleic acid sensing and defects in metabolizing pathways or retroelement control contributing to the breakdown of B cell tolerance.
Article
Immunology
Frederik Staels, Willem Roosens, Simone Giovannozzi, Leen Moens, Jan Bogaert, Cecilia Iglesias-Herrero, Rik Gijsbers, Xavier Bossuyt, Glynis Frans, Adrian Liston, Stephanie Humblet-Baron, Isabelle Meyts, Lucas Van Aelst, Rik Schrijvers
Summary: Autosomal dominant Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations cause an inborn error of immunity with chronic mucocutaneous candidiasis, recurrent infections, and autoimmune manifestations. Treatment includes antifungal therapy, antibiotics, and immunosuppressive therapy. A case of STAT1 GOF patient with elevated cardiac troponins leading to a diagnosis of idiopathic myocarditis is described. Treatment with a JAK-inhibitor mitigated inflammation but failed to alter fibrosis, leading to fatal arrhythmia.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Cell Biology
Adrian Liston, Anne C. La Flamme, Gabrielle T. Belz, Christopher R. Parish, Judith M. Greer
Summary: This editorial recounts the history of Immunology & Cell Biology journal, from its founding in 1924 to its current focus on immunology research.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Editorial Material
Cell Biology
Adrian Liston
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Editorial Material
Neurosciences
Magda Ali, Adrian Liston
Summary: In vivo CRISPR screen identifies genetic modules that control T cell infiltration in multiple sclerosis, shedding light on the immunopathology of the disease.
NATURE NEUROSCIENCE
(2023)
Review
Urology & Nephrology
Carola G. Vinuesa, Nan Shen, Thuvaraka Ware
Summary: This review examines insights from genetic studies of systemic lupus erythematosus (SLE), including observations from reports of monogenic SLE and the role of common and rare variants. It discusses the importance of age-associated B cells in SLE and how genetic, epigenetic, and transcriptomic data suggest their key role in the disease. Recent studies have provided valuable information on the genetic architecture of SLE through genome-wide association studies (GWAS) and sequencing studies. While monogenic SLE accounts for a small proportion of cases, it has been instrumental in understanding disease mechanisms. The review also highlights the role of nucleic acid sensing and autoimmune response in SLE development, and the potential of targeted therapies using bespoke models of disease.
NATURE REVIEWS NEPHROLOGY
(2023)
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
Biochemical Research Methods
Carlos P. Roca, Oliver T. Burton, Julika Neumann, Samar Tareen, Carly E. Whyte, Vaclav Gergelits, Rafael V. Veiga, Stephanie Humblet-Baron, Adrian Liston
Summary: The development of dimensionality-reduction tools is necessary for handling high-dimensional single-cell data. t-SNE and UMAP are frequently used approaches that provide clear visualization of complex single-cell datasets. However, their limited use as visualization tools is due to the lack of robust statistical approaches. In this study, a statistical test based on the Kolmogorov-Smirnov test is proposed to evaluate the difference between dimensionality-reduced datasets. This test utilizes the inter-relationship of single cells for comparison, resulting in a robust statistic that can identify true biological variation and provide a valid distance between single-cell datasets.
CELL REPORTS METHODS
(2023)
Article
Immunology
Julika Neumann, Erika Van Nieuwenhove, Lara E. Terry, Frederik Staels, Taylor R. Knebel, Kirsten Welkenhuyzen, Kourosh Ahmadzadeh, Mariah R. Baker, Margaux Gerbaux, Mathijs Willemsen, John S. Barber, Irina I. Serysheva, Liesbeth De Waele, Francois Vermeulen, Susan Schlenner, Isabelle Meyts, David Yule, Geert Bultynck, Rik Schrijvers, Stephanie Humblet-Baron, Adrian Liston
Summary: Calcium signaling is crucial for lymphocyte activation, and disruptions of store-operated calcium entry can lead to severe immunodeficiency. In this study, genetic variations of the ITPR3 gene were identified in two Caucasian patients with immunodeficiency, indicating a potential link between these variations and impaired immune responses. The findings demonstrate the functional connection between defective endoplasmic reticulum calcium channels and immunodeficiency, highlighting the importance of IP(3)Rs as diagnostic targets for patients with specific inborn errors of immunity.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)