Review
Immunology
Im-Hong Sun, Eva Gillis-Buck, Tippi C. Mackenzie, James M. Gardner
Summary: This review discusses the importance of maternal immune tolerance to fetal and placental tissues during pregnancy and the role of autoimmune regulator (Aire) in this process. Recent studies have identified various populations of Aire-expressing cells in secondary lymphoid organs, which contribute to the maintenance of maternal-fetal tolerance. Deletion of these cells during pregnancy leads to T-cell activation and lymphocytic infiltration of the uterus, resulting in pregnancy complications.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Immunology
Eva Gillis-Buck, Haleigh Miller, Marina Sirota, Stephan J. Sanders, Vasilis Ntranos, Mark S. Anderson, James M. Gardner, Tippi C. MacKenzie
Summary: Research showed that depletion of Aire(+) cells during pregnancy leads to an expansion of activated T cells, particularly T follicular helper cells. The elimination of Aire-expressing cells results in immune-mediated intrauterine growth restriction (IUGR), indicating a previously undescribed mechanism for the maintenance of maternal-fetal immune homeostasis.
SCIENCE IMMUNOLOGY
(2021)
Review
Immunology
Min Hu, Natasha M. Rogers, Jennifer Li, Geoff Y. Zhang, Yuan Min Wang, Karli Shaw, Philip J. O'Connell, Stephen Alexander
Summary: Tregs play a crucial role in kidney transplantation by limiting immune activation and potentially reducing the need for immunosuppression. Studies have shown their importance in improving allo-specific Treg function in both animal and human models.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Romy Steiner, Nina Pilat
Summary: Since the discovery of regulatory T cells (Tregs) as crucial regulators of immune tolerance, they have become a promising tool for inducing donor-specific tolerance in transplantation medicine. Various approaches, such as adoptive transfer, ex vivo expansion, and in vivo stimulation, have been explored to enhance Treg therapy. Furthermore, next generation concepts, such as CARs, TRUCKs, and BARs, are being investigated for improving Treg function. Clinical trials have shown promise, but long-term results and efficacy remain limited, and challenges for clinical translation remain open.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Immunology
Gustaaf G. van Laar, Jan Piet van Hamburg, Sander W. Tas
Summary: Auto-immune regulator (AIRE) is a transcription factor mainly found in the thymus, but recent studies have identified its expression in other tissues as well. The exact function of these extrathymic AIRE expressing cells (eTACs) is still unknown, but they have the potential to modulate or inhibit immune responses, making them promising targets for restoring tolerance in autoimmune diseases or improving immuno-therapy in cancer settings.
AUTOIMMUNITY REVIEWS
(2022)
Article
Immunology
Yonghong Zhang, Huiyan Wang, Panpan Qiu, Jingwen Jiang, Xuhong Wu, Jie Mei, Haixiang Sun
Summary: Placental trophoblasts play a role in the regulation of regulatory T cells through the PD-1/PD-L1 pathway, and decreased expression of PD-L1 in trophoblasts is associated with Treg deficiency in pregnancy failure. YY1 modulates the expression of PD-L1 in trophoblasts, and elevated levels of NO from M1 macrophages may lead to reduced YY1 expression in recurrent miscarriage.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Naomi Benne, Danielle ter Braake, Arie Jan Stoppelenburg, Femke Broere
Summary: This article discusses the strategy of using nanoparticles to deliver antigens and restore immune tolerance. It highlights potential cell targets and application methods for nanoparticles, as well as how nanoparticles carrying immunomodulators can activate tolerance in other antigen-presenting cell types. It also emphasizes the importance of considering relevant factors when translating animal studies to clinical applications.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Severine Menoret, Laurent Tesson, Severine Remy, Victor Gourain, Celine Serazin, Claire Usal, Aude Guiffes, Vanessa Chenouard, Laure-Helene Ouisse, Malika Gantier, Jean-Marie Heslan, Cynthia Fourgeux, Jeremie Poschmann, Carole Guillonneau, Ignacio Anegon
Summary: In this study, a Foxp3-EGFP rat transgenic line was created to genetically tag CD4(+) and CD8(+) FOXP3(+) regulatory T cells. CD4(+)EGFP(+) Treg were found to be 5-10 times more frequent than CD8(+)EGFP(+) Treg. RNAseq analysis provided insights into the transcriptome of CD8(+) Treg, allowing for a better understanding of their phenotype and function.
Review
Immunology
Jeffrey A. Bluestone, Brent S. McKenzie, Joshua Beilke, Fred Ramsdell
Summary: Regulatory T (Treg) cells play a crucial role in maintaining peripheral tolerance and preventing various immune-related diseases. They are able to develop in both the thymus and peripheral tissues through the expression of a transcription factor called FOXP3. Treg cells exert their tolerogenic effects by using multiple mechanisms, such as producing inhibitory cytokines, suppressing T effector cells, and modulating antigen-presenting cell function. Recently, there has been a focus on genetically engineering Treg cells to enhance their therapeutic potential, leading to ongoing clinical trials. This review highlights the advancements and challenges in harnessing Treg cells as a new approach for treating diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Jiaxi Wang, Caleb A. Lareau, Jhoanne L. Bautista, Alexander R. Gupta, Katalin Sandor, Joe Germino, Yajie Yin, Matthew P. Arvedson, Gabriella C. Reeder, Nathan T. Cramer, Fang Xie, Vasilis Ntranos, Ansuman T. Satpathy, Mark S. Anderson, James M. Gardner
Summary: The study defines eTACs at the transcriptional, genomic, and proteomic level using single-cell multiomics, transgenic murine models, and functional approaches. It reveals that eTACs consist of migratory dendritic cells expressing CCR7(+) Aire and a population coexpressing Aire and RORγt, termed Janus cells, with highly accessible chromatin and broad gene expression. Transgenic self-antigen expression by eTACs induces negative selection and prevents autoimmune diabetes, highlighting a core program influencing self-representation and tolerance in immune development.
SCIENCE IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Michel Y. Braun
Summary: T cells, particularly T lymphocytes of the immune system, exhibit characteristics of proliferation and mobility in tissues and organs, requiring metabolic plasticity to fulfill their immune function. This review focuses on the various mechanisms that allow T cells to adapt their metabolism to different real-life circumstances, such as exiting quiescence, differentiating into effector cells, and participating in immune memory formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Nina Pilat, Romy Steiner, Jonathan Sprent
Summary: The limited success of solid organ transplantation is influenced by the insufficiency of immunosuppressive regimens to control chronic rejection and late graft loss. However, regulatory T cells (Tregs) have shown potential in inducing allograft tolerance and prolonging graft survival. The first Treg-based clinical trials have yielded promising results, demonstrating the feasibility and safety of Treg therapy in organ transplantation. Nevertheless, there are still unresolved questions regarding Treg phenotype, dosage, antigen-specificity, adjunct immunosuppressants, and efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Sebastien This, Stefanie F. Valbon, Marie-Eve Lebel, Heather J. Melichar
Summary: T cell tolerance is tightly regulated by various mechanisms, with the strength of antigen receptor signaling influencing the fate and immune response of autoreactive T cells. Understanding and manipulating this signaling strength can have significant clinical implications for autoimmune diseases and immunotherapy outcomes.
Article
Immunology
Jan Dobes, Osher Ben-Nun, Amit Binyamin, Liat Stoler-Barak, Bergithe E. Oftedal, Yael Goldfarb, Noam Kadouri, Yael Gruper, Tal Givony, Itay Zalayat, Katarina Kovacova, Helena Bohmova, Evgeny Valter, Ziv Shulman, Dominik Filipp, Eystein S. Husebye, Jakub Abramson
Summary: Research has found that Aire(+)MHCII(+) type 3 innate lymphoid cells play a critical role in sensing and presenting Candida albicans, and they have a significant impact on the generation of Candida-specific T(H)17 cells.
Article
Immunology
Esther Bernaldo-de-Quiros, Beatriz Cozar, Rocio Lopez-Esteban, Maribel Clemente, Juan Miguel Gil-Jaurena, Carlos Pardo, Ana Pita, Ramon Perez-Caballero, Manuela Camino, Nuria Gil, Maria Eugenia Fernandez-Santos, Susana Suarez, Marjorie Pion, Marta Martinez-Bonet, Rafael Correa-Rocha
Summary: Regulatory T cells (Treg) are a promising therapy for controlling inflammation. Umbilical cord blood and discarded pediatric thymus have been proposed as alternative sources of Treg. A novel manufacturing protocol has been developed to obtain high-quality and high-quantity Treg from pediatric thymus, which shows potential for cellular therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
