Review
Biochemistry & Molecular Biology
Ting-Ting Sheu, Bor-Luen Chiang
Summary: This review discusses the critical role of immune homeostasis in defending against pathogens and preventing self-reactivity, as well as how defects in this system can lead to autoimmune diseases. It emphasizes the significance of lymphopenia and lymphopenia-induced proliferation in normal and autoimmune conditions, highlighting their importance in autoimmune diseases. The review also underscores the crucial role of regulatory T cells in autoimmune conditions, positioning them as key therapeutic targets for autoimmunity treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Soo Jung Yang, Akhilesh K. Singh, Travis Drow, Tori Tappen, Yuchi Honaker, Fariba Barahmand-Pour-Whitman, Peter S. Linsley, Karen Cerosaletti, Kelsey Mauk, Yufei Xiang, Jessica Smith, Emma Mortensen, Peter J. Cook, Karen Sommer, Iram Khan, Denny Liggitt, David J. Rawlings, Jane H. Buckner
Summary: The adoptive transfer of engineered T-regs (EngT(regs)) specific to islet antigens shows therapeutic potential in preventing type 1 diabetes by suppressing both effector T cells recognizing the same islet antigen and bystander effector T cells. EngT(regs) can home to the pancreas and block diabetes triggered by specific or polyclonal effector T cells. This approach demonstrates the promise of antigen-specific EngT(regs) as a targeted therapy for T1D.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Immunology
Kai Yang
Summary: Regulatory T cells (Tregs) play important roles in immune regulation, and cellular metabolism is crucial for their function. Tregs reprogram cellular metabolic programs to sustain their suppressive function, and altered metabolism also influences Treg activation and function. Manipulation of systemic metabolites has emerged as an attractive strategy to modulate tissue Treg metabolism and improve treatment of immune-related diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
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)
Review
Urology & Nephrology
Charles G. Rickert, James F. Markmann
Summary: Solid organ transplantation has been successful in immunosuppression, but there are significant costs and challenges. Immunosuppression and tolerance based on regulatory T cells provide an attractive alternative.
SEMINARS IN NEPHROLOGY
(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
Jose M. Gonzalez-Navajas, Dengxia Denise Fan, Shuang Yang, Fengyuan Mandy Yang, Beatriz Lozano-Ruiz, Liya Shen, Jongdae Lee
Summary: Cancer arises from genetic mutations allowing cells to proliferate uncontrollably, but the failure of anticancer immunity, influenced by the tumor environment's impact on T cells, is essential for cancer survival. Immune checkpoint inhibitor therapy was developed to combat the immune paralysis induced by tumor environments, specifically by targeting molecules like PD-1. While effector T cells work to eliminate cancers, Tregs in the tumor environment suppress native anticancer immunity and reduce the efficacy of ICI therapies. Targeted efforts to deplete tumor-associated Tregs are underway to enhance ICI therapy effectiveness without causing systemic autoimmune responses. Understanding the roles of Tregs in anti-cancer immunity and ICI therapies can lead to more precise targeting of intratumoral Tregs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jie Sun, Guang-Peng Zhou, Shi-Peng Li, Xiao-Jie Chen, Jin-Ming Zhang, Yi-Zhou Jiang, Bin Cui, Hai-Ming Zhang, Li-Ying Sun, Zhi-Jun Zhu
Summary: The role of ILC2s in acute rejection after liver transplantation remains unclear. This study found that hepatic ILC2s were significantly increased in rejection cases compared to non-rejection cases, and there was a close correlation between hepatic ILC2s and Treg cells. The number of allograft infiltrating ILC2s may play inhibitory roles in posttransplant immune homeostasis, favoring resolution of liver allograft rejection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Agnieszka Goral, Malgorzata Firczuk, Klaudyna Fidyt, Marta Sledz, Francesca Simoncello, Karolina Siudakowska, Giulia Pagano, Etienne Moussay, Jerome Paggetti, Patrycja Nowakowska, Stefania Gobessi, Joanna Barankiewicz, Aleksander Salomon-Perzynski, Federica Benvenuti, Dimitar G. Efremov, Przemyslaw Juszczynski, Ewa Lech-Maranda, Angelika Muchowicz
Summary: Regulatory T cells (Tregs) play an important role in chronic lymphocytic leukemia (CLL) by inhibiting the activation and function of T cells, affecting the immune response. This study identified a specific Tregs subpopulation in CLL with a phenotype and gene expression profile supportive of leukemia survival and proliferation. Tregs depletion triggered the expansion of anti-leukemic cytotoxic T cell clones, leading to leukemia eradication. In addition, inhibiting Tregs showed therapeutic benefits in CLL treatment, either as monotherapy or in combination with an immune checkpoint inhibitor.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Rashi Sehgal, Rakhi Maiwall, Vijayaraghavan Rajan, Mojahidul Islam, Sukriti Baweja, Navkiran Kaur, Guresh Kumar, Gayatri Ramakrishna, Shiv K. Sarin, Nirupma Trehanpati
Summary: In cirrhosis patients with sepsis, MDSCs expand and inhibit immune response by increasing FOXP3(+)Tregs and suppressing CD4(+) T-cell proliferation. GM-CSF therapy can suppress MDSCs, improve T-cell functionality, and reduce the presence of Tregs.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Zheng Zhang, Jihua Guo, Rong Jia
Summary: Treg plasticity is associated with inflammatory diseases and cancers. Regulating Treg plasticity is a promising direction for the treatment of inflammatory diseases and cancers.
INFLAMMATION RESEARCH
(2023)
Article
Genetics & Heredity
Sabine Muth, Annekatrin Klaric, Markus Radsak, Hansjoerg Schild, Hans Christian Probst
Summary: Treg-expressed CD27 maintains DC tolerogenic in steady state and limits anti-tumor immunity; Ablation of Treg-expressed CD27 synergizes with PD-1 blockade to improve CTL-mediated tumor control.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Immunology
Pierre Henschel, Sybille Landwehr-Kenzel, Niklas Engels, Andrea Schienke, Jakob Kremer, Tobias Riet, Nella Redel, Konstantinos Iordanidis, Valerie Saetzler, Katharina John, Miriam Heider, Matthias Hardtke-Wolenski, Heiner Wedemeyer, Elmar Jaeckel, Fatih Noyan
Summary: Researchers have developed an HLA-A2specific CAR vector that co-expresses FOXP3, which can increase the safety and efficacy of CAR-Treg products. Stable expression of FOXP3 in Tregs prevents conversion into pathogenic T effector cells under pro-inflammatory conditions.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Immunology
Isabelle Serr, Felix Drost, Benjamin Schubert, Carolin Daniel
Summary: This review discusses the potential and challenges of antigen-specific Treg therapies in allergy and autoimmune diseases, with a focus on type 1 diabetes. It also highlights recent advances in miRNA-targeting and computational strategies for promoting Tregs and analyzing tissue-specific Tregs at the single-cell level.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Marta Vuerich, Na Wang, Ahmadreza Kalbasi, Jonathon J. Graham, Maria Serena Longhi
Summary: Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by hypergammaglobulinemia, presence of serum autoantibodies, and histological features of interface hepatitis. Corticosteroids, azathioprine, and other immunosuppressants are the main therapeutic options, but withdrawal of immunosuppression may lead to disease relapse. Understanding the pathogenesis of AIH is crucial for developing more effective treatments.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
L. S. K. Walker, M. von Herrath
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Myriam Chimen, Helen M. McGettrick, Bonita Apta, Sahithi J. Kuravi, Clara M. Yates, Amy Kennedy, Arjun Odedra, Mohammed Alassiri, Matthew Harrison, Ashley Martin, Francesca Barone, Saba Nayar, Jessica R. Hitchcock, Adam F. Cunningham, Karim Raza, Andrew Filer, David A. Copland, Andrew D. Dick, Joseph Robinson, Neena Kalia, Lucy S. K. Walker, Christopher D. Buckley, Gerard B. Nash, Parth Narendran, G. Ed Rainger
Editorial Material
Immunology
Lucy S. K. Walker
TRENDS IN IMMUNOLOGY
(2015)
Review
Immunology
Lucy S. K. Walker, David M. Sansom
TRENDS IN IMMUNOLOGY
(2015)
Article
Infectious Diseases
Tonney S. Nyirenda, Malcolm E. Molyneux, Rupert Kenefeck, Lucy S. K. Walker, Calman A. MacLennan, Robert S. Heyderman, Wilson L. Mandala
JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY
(2015)
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
Medicine, Research & Experimental
Rupert Kenefeck, Chun Jing Wang, Tauseef Kapadi, Lukasz Wardzinski, Kesley Attridge, Louise E. Clough, Frank Heuts, Alexandros Kogimtzis, Sapna Patel, Miranda Rosenthal, Masahiro Ono, David M. Sansom, Parth Narendran, Lucy S. K. Walker
JOURNAL OF CLINICAL INVESTIGATION
(2015)
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)
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
Oncology
Vinodh Kannappan, Kate Butcher, Malgorzata Trela, Iain Nicholl, Weiguang Wang, Kesley Attridge
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2017)