Article
Immunology
Chiung-Ya Chen, Yun-Fen Hung, Ching-Yen Tsai, Yi-Chun Shih, Ting-Fang Chou, Ming-Zong Lai, Ting-Fang Wang, Yi-Ping Hsueh
Summary: This study reveals the differential impacts of TLR3 and TLR7 signaling pathways on transcriptomic profiles in bone marrow-derived macrophages. Activation of TLR3 enhances innate immunity globally, while TLR7 signaling disrupts downstream signaling leading to the expression of cytokines and chemokines. Overall, TLR3 and TLR7 display different properties and provide useful mouse models for further investigation of these RNA-sensing TLRs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Daria Bortolotti, Valentina Gentili, Sabrina Rizzo, Giovanna Schiuma, Silvia Beltrami, Giovanni Strazzabosco, Mercedes Fernandez, Francesca Caccuri, Arnaldo Caruso, Roberta Rizzo
Summary: (3) Our study demonstrated that both TLR3 and TLR7 play a role in regulating innate immunity during lung SARS-CoV-2 infection. Activation of TLRs led to the production of pro-inflammatory cytokines and interferons, indicating their potential as targets for early-stage infection control.
Article
Multidisciplinary Sciences
Jaedeok Kwon, Maria Suessmilch, Alison McColl, Jonathan Cavanagh, Brian J. Morris
Summary: Exposure to infection in utero can increase the risk of psychiatric diseases in later life, with different effects observed between double-stranded virus mimetics and single-stranded virus mimetics. Single-stranded virus mimetics induced a more pronounced immune response in pregnant mice and had significant implications for modeling diseases in offspring where maternal virus exposure contributes to environmental disease risk.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Zachary C. Stensland, John C. Cambier, Mia J. Smith
Summary: Targeted therapies focusing on autoantigen-specific B cells have shown potential for more precise treatment of autoimmune disorders, while also presenting challenges that need to be addressed for their clinical applicability.
Article
Biochemistry & Molecular Biology
Gyan Prakash Mishra, Atimukta Jha, Abdul Ahad, Kaushik Sen, Aishwarya Sen, Sreeparna Podder, Subhasish Prusty, Viplov Kumar Biswas, Bhawna Gupta, Sunil Kumar Raghav
Summary: In this study, the researchers conducted a comprehensive epigenomic analysis of murine conventional type-I dendritic cells (cDC1) under different Toll-like receptor (TLR) ligation conditions. They found that NCoR1 plays a role in controlling TLR9 and TLR3-specific responses by regulating enhancer activity and gene expression.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Grant J. Brown, Pablo F. Canete, Hao Wang, Arti Medhavy, Josiah Bones, Jonathan A. Roco, Yuke He, Yuting Qin, Jean Cappello, Julia I. Ellyard, Katharine Bassett, Qian Shen, Gaetan Burgio, Yaoyuan Zhang, Cynthia Turnbull, Xiangpeng Meng, Phil Wu, Eun Cho, Lisa A. Miosge, T. Daniel Andrews, Matt A. Field, Denis Tvorogov, Angel F. Lopez, Jeffrey J. Babon, Cristina Aparicio Lopez, Africa Gonzalez-Murillo, Daniel Clemente Garulo, Virginia Pascual, Tess Levy, Eric J. Mallack, Daniel G. Calame, Timothy Lotze, James R. Lupski, Huihua Ding, Tomalika R. Ullah, Giles D. Walters, Mark E. Koina, Matthew C. Cook, Nan Shen, Carmen de Lucas Collantes, Ben Corry, Michael P. Gantier, Vicki Athanasopoulos, Carola G. Vinuesa
Summary: Enhanced Toll-like receptor 7 (TLR7) signaling has been associated with human systemic autoimmune disease, but evidence of TLR7 gene variants causing lupus is lacking. In this study, researchers identified a newly described TLR7(Y264H) variant that increased sensing of guanosine and 2',3'-cGMP and was sufficient to cause lupus in mice. Enhanced TLR7 signaling was shown to drive aberrant B cell survival and the accumulation of specific B cell subsets, while deficiency of the downstream adapter protein MyD88 rescued autoimmunity and all phenotypes. The study highlights the importance of TLR7 and guanosine-containing self-ligands in the pathogenesis of lupus and suggests potential therapeutic targets.
Article
Multidisciplinary Sciences
Timm Amendt, Gabriele Allies, Antonella Nicolo, Omar El Ayoubi, Marc Young, Tamas Roszer, Corinna S. Setz, Klaus Warnatz, Hassan Jumaa
Summary: Hormone production is crucial for maintaining metabolic homeostasis. This study found that antibody-deficient mice and immunodeficiency patients have lower blood glucose concentrations. The presence of insulin-specific IgG antibodies in total IgG preparations and healthy individuals' serum is necessary for restoring blood glucose physiology. Autoreactive IgM antibodies recognizing insulin play a key role in regulating blood glucose and metabolism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Wenjie Zuo, Mai Wakimoto, Noriyasu Kozaiwa, Yutaro Shirasaka, Seong-Wook Oh, Shiori Fujiwara, Hitoshi Miyachi, Amane Kogure, Hiroki Kato, Takashi Fujita
Summary: RIG-I-like receptors, protein kinase R, and endosomal Toll-like receptor 3 are important in sensing viral RNA and determining cell fate. Short 5'-triphosphate dsRNA induces slow apoptosis dependent on IRF-3 and IFN-I, while intracellular long dsRNA is sensed by PKR and TLR3, which activate distinct signals and synergistically induce rapid apoptosis.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Rui Jiang, Wentao Zhu, Zhiwei Liao, Chunrong Yang, Jianguo Su
Summary: TLR7 plays a crucial role in sensing viral ssRNA and dsRNA, but there are differences in the mechanism of dsRNA sensing between fish and tetrapods.
Article
Toxicology
Zihuan Li, Hang Yu, Meiqi Song, Hansruedi Glatt, Jianjun Liu, Yungang Liu
Summary: The study found that 1-MP and its metabolite have different effects on cells depending on exposure time and concentration, including inducing centromere-positive micronuclei along with mitotic arrest and spindle aberrations. The chromosome-damaging mechanism is influenced by the exposure regime and concentration levels.
ARCHIVES OF TOXICOLOGY
(2021)
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)
Article
Oncology
Richard J. Bende, Linda M. Slot, Mark J. Kwakkenbos, Thera A. M. Wormhoudt, Aldo Jongejan, Gwenny M. Verstappen, Antoine C. M. van Kampen, Jeroen E. J. Guikema, Frans G. M. Kroese, Carel J. M. van Noesel
Summary: We found that normal memory B lymphocytes have a significant number of de novo mutations in the genome. In this study, we analyzed the somatic mutations in memory B cells expressing autoreactive rheumatoid factor (RF) from patients with Sjogren's syndrome (SS). The de novo exome mutations in RF B cells were different from those in healthy donor memory B cells, with a higher number of mutations and enrichment in genes mutated in B-cell non-Hodgkin lymphomas. Additionally, one SS patient developed diffuse large B-cell lymphoma (DLBCL) from an RF precursor clone identified 2 years earlier. Our findings provide new insights into the early stages of B-cell derailment and lymphomagenesis.
JOURNAL OF PATHOLOGY
(2023)
Article
Cell Biology
Joseph Bisaccia, Swann Meyer, Adrien Bertrand-Chapel, Quentin Hecquet, Virginie Barbet, Bastien Kaniewski, Sophie Leon, Nicolas Gadot, Isabelle Rochet, Iveta Fajnorova, Pierre Leblond, Martine Cordier-Bussat, Nadege Corradini, Alexandre Vasiljevic, Marc Billaud, Cecile Picard, Laura Broutier, Cindy Gallerne, Aurelie Dutour, Jean-Yves Blay, Marie Castets
Summary: Toll-like receptor 3 (TLR3) is a pattern recognition receptor that plays a role in the innate immune response to infection. It has shown potential in anti-tumor effects and is being tested in clinical trials for adult cancers. However, its role in childhood cancers has not been evaluated. This study reveals that high TLR3 expression is associated with a better prognosis in childhood sarcomas and demonstrates the therapeutic potential of targeting TLR3 in pediatric sarcomas.
CELL DEATH DISCOVERY
(2023)
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.
Review
Cell Biology
Carlo G. Bonasia, Wayel H. Abdulahad, Abraham Rutgers, Peter Heeringa, Nicolaas A. Bos
Summary: This article discusses the key role of autoreactive B cells in autoimmune diseases, the use of novel techniques to identify these cells, and potential therapeutic strategies. The mechanisms underlying the development of autoreactive B cells are still not fully understood.
