Article
Immunology
Charles Kyriakos Vorkas, Chirag Krishna, Kelin Li, Jeffrey Aube, Daniel W. Fitzgerald, Linas Mazutis, Christina S. Leslie, Michael S. Glickman
Summary: This study provides an integrated single-cell transcriptomic analysis of human MAIT cells, revealing their phenotypic and functional heterogeneity and complex roles in health and disease. The study shows that MAIT cells exhibit a wide range of phenotypes, including homeostatic, effector, helper, tissue-infiltrating, regulatory, and exhausted phenotypes, with distinct gene expression programs associated with CD4(+) or CD8(+) coexpression. Early activation of MAIT cells leads to the rapid adoption of a cytotoxic phenotype, while prolonged stimulation induces heterogeneous states defined by proliferation, cytotoxicity, immune modulation, and exhaustion. Furthermore, a subset of MAIT cells expressing FOXP3, resembling conventional regulatory T cells, was identified. The presence of MAIT cell subpopulations in individuals recently exposed to Mycobacterium tuberculosis confirms their role during human infection. This study provides important insights into the functional heterogeneity of MAIT cells and their potential implications in immune responses and disease development.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Katherine A. Freitas, Julia A. Belk, Elena Sotillo, Patrick J. Quinn, Maria C. Ramello, Meena Malipatlolla, Bence Daniel, Katalin Sandor, Dorota Klysz, Jeremy Bjelajac, Peng Xu, Kylie A. Burdsall, Victor Tieu, Vandon T. Duong, Micah G. Donovan, Evan W. Weber, Howard Y. Chang, Robbie G. Majzner, Joaquin M. Espinosa, Ansuman T. Satpathy, Crystal L. Mackall
Summary: This research identified MED12 and CCNC as key genes controlling T cell function through CRISPR knockout screening. Knockout of MED12 gene enhances antitumor activity, prolongs the effector phenotype of CAR-T and TCR-T cells, and promotes the expansion of non-engineered T cells. The study reveals the importance of Mediator in T cell effector programming and provides a new target to enhance the potency of antitumor T cell responses.
Review
Immunology
Matthew Clark, Charles J. Kroger, Qi Ke, Roland M. Tisch
Summary: TCR signaling plays a crucial role in the development of T cells and the formation of self-reactive T cells, particularly in type 1 diabetes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuxin Wang, Thomas W. Carion, Abdul Shukkur Ebrahim, Gabriel Sosne, Elizabeth A. Berger
Summary: The study showed that Tβ4, as an adjunct therapy to ciprofloxacin, can reduce inflammation and enhance host defense by influencing Mφ function in P. aeruginosa-induced keratitis. Infiltration of Mφ and their functional activities were decreased with Tβ4 treatment, suggesting a more efficacious option for treating bacterial keratitis. In vitro studies confirmed the in vivo findings, showcasing the potential of adjunctive Tβ4 therapy in influencing Mφ infiltration, activation, and function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yuxin Wang, Thomas W. Carion, Abdul Shukkur Ebrahim, Gabriel Sosne, Elizabeth A. Berger
Summary: The study showed that adjunctive T beta 4 treatment significantly reduced infiltrated PMNs in infected corneas and suppressed the expression of proinflammatory markers on these cells, leading to a well-controlled production of ROS, NETs, and limited PMN apoptosis. Furthermore, both in vivo and in vitro findings confirmed the potential of adjunctive T beta 4 + ciprofloxacin treatment as a promising option for bacterial keratitis by addressing both the infectious pathogen and cellular-mediated immune response.
Article
Biochemistry & Molecular Biology
Sebastian Wirsching, Michael Fichter, Maximiliano L. Cacicedo, Katharina Landfester, Stephan Gehring
Summary: Cancer is a major cause of death globally. The search for innovative therapies is a key focus in medical research. Vaccine strategies targeting tumor-associated antigens have not yet achieved significant success, possibly due to the tumor microenvironment and regulatory T cells hindering efficacy. ASPH, a potential therapeutic target, is overexpressed in various tumors but minimally expressed in normal tissues. Computer analysis predicts that ASPH has four peptide sequences capable of stimulating regulatory T cell activity. Removing these regulatory T cell epitopes increases effector T cell responses and decreases the overall number of regulatory T cells. These findings suggest that screening and eliminating potential regulatory T cell epitopes can improve the efficacy of new vaccine candidates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Julian Swatler, Laura Turos-Korgul, Marta Brewinska-Olchowik, Sara De Biasi, Wioleta Dudka, Bac Viet Le, Agata Kominek, Salwador Cyranowski, Paulina Pilanc, Elyas Mohammadi, Dominik Cysewski, Ewa Kozlowska, Wioleta Grabowska-Pyrzewicz, Urszula Wojda, Grzegorz Basak, Jakub Mieczkowski, Tomasz Skorski, Andrea Cossarizza, Katarzyna Piwocka
Summary: Leukemic extracellular vesicles play a role in stimulating immunosuppressive Tregs and promoting leukemia growth. The study identifies Rab27a-dependent secretion of leukemic EVs as a potential therapeutic target in myeloid neoplasms.
Article
Immunology
Lomon So, Kazushige Obata-Ninomiya, Alex Hu, Virginia S. Muir, Ayako Takamori, Jing Song, Jane H. Buckner, Ram Savan, Steven F. Ziegler
Summary: We demonstrate that regulatory T cells enforce suppression of CD4 effector T cell activation through active mRNA translational control of the protein synthesis machinery. This study provides evidence that Tregs inhibit global protein synthesis in CD4 effector T cells by regulating mRNAs encoding the translation machinery. These findings highlight the importance of mRNA translational control in enforcing peripheral tolerance.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Immunology
Sara Ness, Shiming Lin, John R. Gordon
Summary: Dendritic cells are antigen-presenting cells that interact with T cells to regulate adaptive immune responses. Under certain conditions, dendritic cells can develop into anti-inflammatory cells, inducing immunologic tolerance. Studies have shown that regulatory dendritic cells induce T cell tolerance by suppressing effector T cells and inducing regulatory T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Sabrina Ceeraz, Charlotte R. Thompson, Richard Beatson, Ernest H. Choy
Summary: T regulatory cell therapy offers a new approach for treating autoimmune diseases and transplantation. CD8(+) Treg cells, particularly the CD8(+)CD28(-) subset, have been shown to be effective in preclinical models, although their impaired functionality in disease limits their effectiveness in immunosuppression. The review focuses on harnessing CD8(+) Treg cell therapy in clinical settings to aid current treatments for autoimmune and inflammatory conditions.
Article
Immunology
Ryan Zander, Moujtaba Y. Kasmani, Yao Chen, Paytsar Topchyan, Jian Shen, Shikan Zheng, Robert Burns, Jennifer Ingram, Can Cui, Nikhil Joshi, Joseph Craft, Allan Zajac, Weiguo Cui
Summary: This study found that CD4(+) T cells consist of three distinct subsets during chronic viral infection, and IL-21 derived from Tfh cells is critical for sustaining CD8(+) T cell responses and viral control.
Article
Biochemistry & Molecular Biology
Daiki Karigane, Miho Haraguchi, Noriko Toyama-Sorimachi, Emi K. Nishimura, Keiyo Takubo
Summary: Thymic dendritic cells (DCs) play a pivotal role in immune tolerance by regulating negative selection of autoreactive T cells in the thymus. This study reveals that the transcription factor Mitf is involved in the regulation of DC homing to the thymus and maintenance of thymic DC population.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Immunology
Michael L. Dixon, Jonathan D. Leavenworth, Jianmei W. Leavenworth
Summary: Regulatory T-cells, particularly effector Tregs (eTregs), play a crucial role in maintaining self-tolerance and tissue homeostasis, with potential implications in tumor development. Understanding the mechanisms that modulate the stability and suppressive function of tumoral Tregs, such as eTregs and T-FR cells, can lead to the development of more effective cancer immunotherapies that target the tumor microenvironment while minimizing systemic side effects.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Jing Lu, Taotao Liang, Ping Li, Qingsong Yin
Summary: The tumor microenvironment (TME) plays a crucial role in various aspects of tumor progression and clinical outcomes. Understanding the status of TME, the involvement of immune cells, and the key factors driving T cell dysfunction is essential for developing effective therapies. This study focuses on the regulatory effects of Interferon regulatory factor 4 (IRF4) on immune cells in the TME and highlights its potential as a therapeutic target for reversing T cell exhaustion and promoting anti-tumor immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
James R. Byrnes, Amy M. Weeks, Eric Shifrut, Julia Carnevale, Lisa Kirkemo, Alan Ashworth, Alexander Marson, James A. Wells
Summary: Immunosuppressive factors in the tumor microenvironment impair T cell function. This study examines how regulatory T cells (Tregs) and hypoxia affect the surface proteome of primary human T cells. The results show that Tregs have only a modest effect on the surface proteome, while hypoxia drastically alters it, inducing an immunosuppressed state.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Immunology
Andrew Jones, Jessica Bourque, Lindsey Kuehm, Adeleye Opejin, Ryan M. Teague, Cindy Gross, Daniel Hawiger
Editorial Material
Immunology
Jessica Bourque, Daniel Hawiger
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Immunology
Jessica Bourque, Daniel Hawiger
Summary: This article reviews the diversity of outcomes and functions of T cells involved in the immunogenic and tolerogenic processes induced by cDC mechanisms in the steady state in murine peripheral lymphoid organs.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jessica Bourque, Adeleye Opejin, Alexey Surnov, Courtney A. Iberg, Cindy Gross, Rajan Jain, Jonathan A. Epstein, Daniel Hawiger
Summary: Hopx is expressed in specific subsets of immune cells and may play crucial roles under multiple immune conditions.
Article
Cell Biology
Courtney A. Iberg, Jessica Bourque, Ian Fallahee, Sungho Son, Daniel Hawiger
Summary: This study reveals that the loss of tolerogenic functions of dendritic cells during immunogenic maturation is mediated by the ablation of the tolerogenic cDC population. The inducer lipopolysaccharide (LPS) triggers the production of tumor necrosis factor (TNF), leading to the acute death of tolerogenic cDCs. This loss is transient and homeostasis is restored through the biological turnover of cDCs in vivo.
Review
Immunology
Jessica Bourque, Daniel Hawiger
Summary: Recombinant immunoglobulins have been used for the past two decades to deliver antigens to dendritic cells, providing critical insights into the mechanisms underlying T cell responses orchestrated by dendritic cells.
Article
Cell Biology
Adeleye Opejin, Alexey Surnov, Ziva Misulovin, Michelle Pherson, Cindy Gross, Courtney A. Iberg, Ian Fallahee, Jessica Bourque, Dale Dorsett, Daniel Hawiger
