Review
Immunology
Jason Cheung, Beata Zahorowska, Michael Suranyi, Jeffrey K. W. Wong, Jason Diep, Stephen T. T. Spicer, Nirupama D. D. Verma, Suzanne J. Hodgkinson, Bruce M. M. Hall
Summary: The immune response to an allograft can activate lymphocytes that cause rejection. The activation of T regulatory cells can reduce allograft rejection and induce immune tolerance. Activated T regulatory cells can be distinguished by various markers. A more detailed characterization of these cells may help reduce non-specific immunosuppression.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Payal Grover, Peeyush N. Goel, Mark I. Greene
Summary: T regulatory cells employ various immunosuppressive mechanisms to limit immune responses, including secretion of cytokines, cell cytolysis, metabolic perturbation, guiding antigen-presenting cell function, etc.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Tiago R. Matos, Masahiro Hirakawa, Ana C. Alho, Lars Neleman, Luis Graca, Jerome Ritz
Summary: CD4(+) Regulatory T cells play a critical role in immune homeostasis, but their heterogeneity in different populations including newborns, healthy adults, and patients after allogeneic hematopoietic stem cell transplantation with or without chronic graft-versus-host disease has been compared. The study found that Treg heterogeneity is higher in adults and gradually increases in the first two years post-transplant, while patients with chronic graft-versus-host disease have significantly fewer distinct Treg subpopulations.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Carsten Riether
Summary: Adult bone marrow hematopoietic stem cells (HSCs) maintain their function through interactions with regulatory T cells (Tregs). In leukemia, these regulatory mechanisms are disrupted, leading to compromised treatment outcomes.
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.
Article
Immunology
Jingnan Liao, Yuan Li, Xiaofeng Li, Xian Su, Jing Peng, Na Xiao, Xiangxiu Fan, Huijun Chen, Guangxiu Lu, Ge Lin, Lamei Cheng, Fei Gong
Summary: The study found that pre-pregnancy blood Treg levels were significantly lower in URPL patients than in controls, and that Treg levels predicted subsequent miscarriages. There were no significant differences among other blood cell types between the two groups.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Fabienne Mazerolles, Frederic Rieux-Laucat
Summary: The expression of co-signalling receptors on T cells plays a crucial role in regulating T cell responses, and an imbalance between activating and inhibitory signals may lead to autoimmunity. Research showed that activated TEFFs and TREGs express different co-signalling receptors, and the expression of PD-L1 on activated TEFFs is correlated with their proliferation.
Article
Immunology
Jessica G. Lee, Kathleen E. Jaeger, Yoichi Seki, Yi Wei Lim, Christina Cunha, Aleksandra Vuchkovska, Alexander J. Nelson, Anya Nikolai, Dan Kim, Michael Nishimura, Katherine L. Knight, Paula White, Makio Iwashima
Summary: The study reveals that a subset of CD14(+) monocytes can generate regulatory Foxp3(+) T-bet(+) T cells from umbilical cord blood, which suppress T-cell proliferation and ameliorate graft-versus-host disease. Additionally, adult peripheral blood monocytes are capable of inducing Foxp3(+) T cells, but their induction is inhibited by lymphoid cells from adult peripheral blood in neonates. This suggests a novel immunoregulatory role of monocytes in generating regulatory T cells with implications for both neonates and adults.
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)
Article
Multidisciplinary Sciences
Pawan K. Gupta, Jennifer B. Allocco, Jane M. Fraipont, Michelle L. McKeague, Peter Wang, Michael S. Andrade, Christine McIntosh, Luqiu Chen, Ying Wang, Yan Li, Jorge Andrade, Jose R. Conejo-Garcia, Anita S. Chong, Maria-Luisa Alegre
Summary: This study investigates the susceptibility of Tconvs to Treg suppression during tolerance induction in transplantation. The findings suggest that transplantation tolerance is associated with an increased sensitivity of alloreactive Tconvs to Treg suppression, which is regulated by the expression of the transcription factor Satb1. Targeting Satb1 could potentially be a strategy to improve transplant outcomes by modulating Treg-sparing immunosuppressive therapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Dao X. Nguyen, Helen M. Baldwin, Amara N. Ezeonyeji, Mohammed Rohan Butt, Michael R. Ehrenstein
Summary: The study revealed that patients with PsA have an increased Th17:Treg ratio, which can be reversed by anti-TNF therapy. Treg from patients treated with different therapies showed contrasting effects on regulating effector T-cell migration, with TNF blockade boosting Treg suppression of migration.
Article
Biology
Daniil Shevyrev, Valeriy Tereshchenko, Elena Blinova, Nadezda Knauer, Ekaterina Pashkina, Alexey Sizikov, Vladimir Kozlov
Summary: The study revealed that the proliferation of Treg cells in patients with rheumatoid arthritis under HP cytokine stimulation is lower compared to healthy individuals, and the suppressive activity decreases, which may lead to the proliferation of self-reactive T cell clones.
Article
Immunology
Shi-Peng Li, Jin-Ming Zhang, Xiao-Jie Chen, Guang-Peng Zhou, Jie Sun, Bin Cui, Liu-Xin Zhou, Hai-Ming Zhang, Wei-Tao Que, Li-Ying Sun, Zhi-Jun Zhu
Summary: DPT cells are increased in liver transplant patients, especially in rejection cases. These cells show contiguity with Treg cells and their exhaustion is enhanced by increased PD-1 expression. These findings suggest that DPT cells may play a role in immune tolerance and could be targeted for preventing liver transplant rejection.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Murilo Delgobo, Emil Weiss, DiyaaElDin, Ashour Leon Richter, Lisa Popiolkowski, Panagiota Arampatzi, Verena Stangl, Paula Arias-Loza, Encarnita Mariotti-Ferrandiz, Peter P. Rainer, Antoine-Emmanuel Saliba, Burkhard Ludewig, Ulrich Hofmann, Stefan Frantz, Gustavo Campos Ramos
Summary: In this study, the researchers investigated how antigen-specific T-helper cells differentiate in the myocardial environment. They used a transgenic T cell receptor model and single-cell transcriptomics to study the cells in the murine infarcted myocardium. The results showed that these cells acquired a regulatory phenotype and influenced tissue repair.
CIRCULATION RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Tyler C. Moore, Kim J. Hasenkrug
Summary: B lymphocytes play important roles during viral infections by producing antibodies, acting as antigen-presenting cells, regulating immune responses, and inducing Tregs. In the Friend virus model, Tregs inhibit effector CD8+ T-cell responses and contribute to virus persistence. Research focuses on the interactions between B cells and Tregs during FV infection.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Jasmin Ochs, Nitzan Nissimov, Sebastian Torke, Marie Freier, Katja Grondey, Julian Koch, Matthias Klein, Linda Feldmann, Cathrin Gudd, Tobias Bopp, Silke Haeusser-Kinzel, Martin S. Weber
Summary: The study found that CD20(+) T cells acquire CD20 from B cells via trogocytosis and interaction with B cells leads to activation, indicating high pathogenic potential. CD20(+) T cells increase during experimental autoimmune encephalomyelitis (EAE), and eliminating CD20(+) T cells can effectively ameliorate EAE.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Monika Bednarczyk, Vanessa Bolduan, Maximilian Haist, Henner Stege, Christoph Hieber, Lisa Johann, Carsten Schelmbauer, Michaela Blanfeld, Khalad Karram, Jenny Schunke, Tanja Klaus, Ingrid Tubbe, Evelyn Montermann, Nadine Roehrig, Maike Hartmann, Jana Schlosser, Tobias Bopp, Bjoern E. Clausen, Ari Waisman, Matthias Bros, Stephan Grabbe
Summary: This study generated a mouse model with a knockout of the CD18 gene specifically in dendritic cells, and found that it affected cytokine production, signal transduction, and inflammatory signaling. In a mouse model of experimental autoimmune encephalomyelitis, the knockdown of beta 2 integrins in dendritic cells resulted in a delayed onset and milder course of the disease, associated with lower frequencies of Th1/Th17 cells in the spinal cord.
Article
Immunology
Bjoern E. Clausen, Lukas Amon, Ronald A. Backer, Luciana Berod, Tobias Bopp, Anna Brand, Sven Burgdorf, Luxia Chen, Meihong Da, Ute Distler, Regine J. Dress, Diana Dudziak, Charles-Antoine Dutertre, Christina Eich, Anna Gabele, Melanie Geiger, Florent Ginhoux, Lucila Giusiano, Gloria J. Godoy, Ahmed E. Hamouda, Lukas Hatscher, Lukas Heger, Gordon F. Heidkamp, Lola C. Hernandez, Lukas Jacobi, Tomasz Kaszubowski, Wan Ting Kong, Christian H. K. Lehmann, Tamara Lopez-Lopez, Karsten Mahnke, Dominik Nitsche, Jorg Renkawitz, Rifat A. Reza, Pablo J. Saez, Laura Schlautmann, Madeleine T. Schmitt, Anna Seichter, Malte Sielaff, Tim Sparwasser, Patrizia Stoitzner, Giorgi Tchitashvili, Stefan Tenzer, Nounagnon R. Tochoedo, Damir Vurnek, Fabian Zink, Thomas Hieronymus
Summary: This article provides a collection of protocols for the functional characterization of mouse and human dendritic cells (DC), including endocytosis and metabolism analysis, transcriptomic and proteomic characterization, migration characterization, and measurement of inflammasome and antigen (cross)-presentation activity. These protocols, written by experienced scientists and peer-reviewed by leading experts, are essential resources for basic and clinical DC immunologists.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Letter
Dermatology
Sabrina Muecklich, Khuram Shehzad, Jessica Tiemann, Li Li, Sonja Leson, Peter J. Nelson, Richard Jennemann, Matthias Klein, Christian Becker, Roger Sandhoff, Kerstin Steinbrink, Verena K. Raker
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Tanja Klaus, Alicia S. Wilson, Elisabeth Vicari, Eva Hadaschik, Matthias Klein, Sara Salome Clara Helbich, Nadine Kamenjarin, Katrin Hodapp, Jenny Schunke, Maximilian Haist, Florian Butsch, Hans Christian Probst, Alexander H. Enk, Karsten Mahnke, Ari Waisman, Monika Bednarczyk, Matthias Bros, Tobias Bopp, Stephan Grabbe
Summary: Leukocyte adhesion deficiency type 1 (LAD-1) is a rare disease characterized by leukocytosis and high susceptibility to infections. In this study, mice lacking CD18 specifically on regulatory T cells (Treg) were generated to investigate the role of Treg in LAD-1 and autoimmunity. The results demonstrate that LFA-1 on Treg plays a crucial role in maintaining immune homeostasis.
Article
Gastroenterology & Hepatology
Felix Simon Ruben Picard, Veronika Lutz, Anna Brichkina, Felix Neuhaus, Teresa Ruckenbrod, Anna Hupfer, Hartmann Raifer, Matthias Klein, Tobias Bopp, Petra Ina Pfefferle, Rajkumar Savai, Immo Prinz, Ari Waisman, Sonja Moos, Hyun-Dong Chang, Stefan Heinrich, Detlef K. Bartsch, Malte Buchholz, Shiv Singh, Mengyu Tu, Lukas Klein, Christian Bauer, Robert Liefke, Andreas Burchert, Ho-Ryun Chung, Philipp Mayer, Thomas M. Gress, Matthias Lauth, Matthias Gaida, Magdalena Huber
Summary: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and immune cells. In this study, the role of a non-canonical CD8(+) T-cell subpopulation producing IL-17A (Tc17) in PDAC was evaluated.
Review
Biochemistry & Molecular Biology
Tanja Klaus, Alicia Wilson, Michael Fichter, Matthias Bros, Tobias Bopp, Stephan Grabbe
Summary: Regulatory T cells (Treg) are important for peripheral tolerance, and b(2)-integrins play a role in leukocyte migration and signaling. Loss-of-function mutations in CD18 can result in leukocyte adhesion deficiency type-1 (LAD-1) with leukocytosis and recurrent infections. This mini-review discusses the role of LFA-1 in Treg induction, maintenance, and regulatory function using various beta(2)-integrin-deficient mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Priska Jost, Franziska Klein, Benjamin Brand, Vanessa Wahl, Amanda Wyatt, Daniela Yildiz, Ulrich Boehm, Barbara A. A. Niemeyer, Martin Vaeth, Dalia Alansary
Summary: Mitochondria play a crucial role in modulating T cell function through their control of energy production and Ca2+ homeostasis. The mitochondrial Ca2+ uniporter (MCU) regulates Ca2+ signals and affects T cell activation. However, the specific effects of MCU on regulatory CD4 T cells (Treg) and their suppressive potential are still unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Friederike Kirschner, Danielle Arnold-Schild, Christian Leps, Mateusz Krzysztof Lacki, Matthias Klein, Yannic Chen, Annekathrin Ludt, Federico Marini, Can Kucuk, Lara Stein, Ute Distler, Malte Sielaff, Thomas Michna, Kristina Riegel, Krishnaraj Rajalingam, Tobias Bopp, Stefan Tenzer, Hansjoerg Schild
Summary: The analysis of secretome provides important information on intercellular communication and cell behavior in specific tissues. Especially in tumors, secretome data can aid in diagnosis and therapy decisions. Mass spectrometry-based analysis of cell-conditioned media is commonly used for unbiased characterization of cancer secretomes in vitro. Metabolic labeling using azide-containing amino acid analogs facilitates this analysis in the presence of serum. However, these modified analogs may affect protein folding and incorporation into newly synthesized proteins. Combining transcriptome and proteome analysis, we investigate the effects of azidohomoalanine labeling on gene and protein expression. Our findings indicate that AHA labeling induces changes in transcript and protein expression, leading to cellular stress, apoptosis-related pathways, and alteration of secretome composition on a global scale.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Multidisciplinary Sciences
Rajinikanth Gogiraju, Claudius Witzler, Fatemeh Shahneh, Astrid Hubert, Luisa Renner, Magdalena L. Bochenek, Konstantinos Zifkos, Christian Becker, Madhusudhan Thati, Katrin Schaefer
Summary: Obesity promotes endothelial dysfunction, and endothelial cells may actively contribute to the development of obesity and metabolic dysfunction. This study reveals the important role of endothelial leptin receptors in the transport of leptin into the brain and neuronal control of food intake, suggesting organ-specific changes in endothelial cell metabolism.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Enric Mocholi, Laura Russo, Keshav Gopal, Andrew G. Ramstead, Sophia M. Hochrein, Harmjan R. Vos, Geert Geeven, Adeolu O. Adegoke, Anna Hoekstra, Robert M. van Es, Jose Ramos Pittol, Sebastian Vastert, Jared Rutter, Timothy Radstake, Jorg van Loosdregt, Celia Berkers, Michal Mokry, Colin C. Anderson, Ryan M. O'Connell, Martin Vaeth, John Ussher, Boudewijn M. T. Burgering, Paul J. Coffer
Summary: Upon antigen-specific TCR engagement, the generation of extramitochondrial pyruvate is crucial for acetyl-CoA production and subsequent histone acetylation remodeling. PDH-deficient T cells show that PDH-dependent acetyl-CoA production is a rate-limiting step during T cell activation. This study highlights the integration of metabolic and histone-modifying enzymes in CD4+ T cell activation, suggesting a potential therapeutic approach for regulating antigen-driven T cell activation.
Article
Oncology
Veronika Lutz, Veronique M. Hellmund, Felix S. R. Picard, Hartmann Raifer, Teresa Ruckenbrod, Matthias Klein, Tobias Bopp, Rajkumar Savai, Peter Duewell, Corinna U. Keber, Andreas Weigert, Ho-Ryun Chung, Malte Buchholz, Andre Menke, Thomas M. Gress, Magdalena Huber, Christian Bauer
Summary: Signaling through IL18R induces exhaustion of CD8(+) T cells, characterized by expression of coinhibitory receptors and loss of effector function. This exhaustion is mediated by an NLRP3-expressing tumor microenvironment that releases IL18. These findings suggest that NLRP3-mediated IL18R signaling could be a potential target for immunotherapy in pancreatic carcinoma.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Immunology
Tjalf Ziemssen, Eugen Schlegel, Marie Groth, Benjamin Ettle, Tobias Bopp
Summary: Booster vaccinations increase neutralizing antibody titers in ofatumumab-treated patients. A booster is recommended in ofatumumab-treated patients.
Article
Multidisciplinary Sciences
Sabrina Giampaolo, Cristina M. Chiarolla, Konrad Knoepper, Martin Vaeth, Matthias Klein, Azeem Muhammad, Tobias Bopp, Friederike Berberich-Siebelt, Amiya K. Patra, Edgar Serfling, Stefan Klein-Hessling
Summary: In the thymus, the deletion of NFATc1 or its inducible isoforms during the DN stages of thymocyte development leads to an increase in gamma delta thymocytes while alpha beta thymocytes are mostly unaffected. These gamma delta thymocytes upregulate PLZF, the master regulator of NKT cell development, acquiring an NKT gamma delta cell phenotype with higher survival rates. The enhancer E2 is crucial for NFATc1's suppressive function in NKT gamma delta cell formation, translating a strong gamma delta TCR signal into inducible expression of NFATc1 isoforms to control the numbers of NKT gamma delta cells.
