Article
Cell Biology
Joseph W. Dean, Eric Y. Helm, Zheng Fu, Lifeng Xiong, Na Sun, Kristen N. Oliff, Marcus Muehlbauer, Dorina Avram, Liang Zhou
Summary: Ahr acts as a promoter for the differentiation and function of resident memory CD8+ T cells. Ahr deletion diminishes a tumor resident polyfunctional CD8+ T cell population and compromises anti-tumor immunity. AHR in human intestinal intraepithelial CD8+ T cells regulates TRM differentiation and granzyme B production in vitro.
Article
Immunology
Leeana D. Peters, Wen- Yeh, Juan M. Arnoletti, Matthew E. Brown, Amanda L. Posgai, Clayton E. Mathews, Todd M. Brusko
Summary: The autoimmune pathogenesis of T1D involves immune cell infiltration into pancreatic islets. CD8(+) T cells play a primary role in killing insulin-producing beta-cells. This study demonstrates the engineering of human T cells to improve the specificity and function of autoreactive CD8(+) T cells, potentially leading to cellular therapeutics for treating autoimmunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Nicolas Page, Sylvain Lemeille, Ilena Vincenti, Bogna Klimek, Alexandre Mariotte, Ingrid Wagner, Giovanni Di Liberto, Jonathan Kaye, Doron Merkler
Summary: The study characterizes the transcriptional and epigenetic landscape of self-reactive CD8+ T cells in central nervous system autoimmunity, showing that the TOX gene is crucial for the maintenance of self-reactive CD8+ T cells. Continuous exposure to CNS self-antigen sustains TOX levels in self-reactive CD8+ T cells.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Hye Sook Han, Seongju Jeong, Hyunglae Kim, Hyung-Don Kim, A. Reum Kim, Minsuk Kwon, Su-Hyung Park, Chang Gok Woo, Hee Kyung Kim, Ki Hyeong Lee, Sung Pil Seo, Ho Won Kang, Won Tae Kim, Wun-Jae Kim, Seok Joong Yun, Eui-Cheol Shin
Summary: The study evaluated the exhaustion status of CD8(+) tumor-infiltrating lymphocytes (TILs) in bladder cancer patients, and found that TOX-expressing PD-1(high)CD8(+)TILs had the highest expression of immune checkpoint receptors (ICRs) and tumor antigen reactivity.
Article
Multidisciplinary Sciences
David M. Schauder, Jian Shen, Yao Chen, Moujtaba Y. Kasmani, Matthew R. Kudek, Robert Burns, Weiguo Cui
Summary: During acute viral infections, CD8 T cells encounter various antigenic and inflammatory signals, leading to differentiation into memory cells or death. Research has shown that memory precursor effector cells maintain open enhancers for key memory genes, with a high enrichment of E2A binding sites. E2A directly regulates the accessibility of enhancers for memory-related genes, increasing the frequency of memory precursor effector cells and accelerating memory cell formation while reducing short-lived effector cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Sara Alavi, Abdullah Al Emran, Hsin-Yi Tseng, Jessamy C. Tiffen, Helen Marie McGuire, Peter Hersey
Summary: This study explores the role of nicotinamide in preventing and reversing T cell exhaustion, which has important implications for immunotherapy against cancers and viral infections. Nicotinamide supplementation was found to prevent the development of inhibitory receptors in T cells and promote the differentiation of T cells to effector states, suggesting a potential therapeutic strategy for enhancing immune responses.
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
Hematology
Haiyue Niu, Li Yan, Liping Yang, Mengying Zhang, Mengyuan Liu, Jie Ren, Zonghong Shao, Rong Fu, Limin Xing, Huaquan Wang
Summary: TOX expression is increased in PRCA patients, leading to CD8(+) T cell overactivation and decrease in regulatory T cells, which play a critical role in the immune pathogenesis of PRCA.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Marija Mojic, Kiyomi Shitaoka, Chikako Ohshima, Sisca Ucche, Fulian Lyu, Hiroshi Hamana, Hideaki Tahara, Hiroyuki Kishi, Yoshihiro Hayakawa
Summary: By analyzing the immunological status of tumor antigen-specific CD8(+) T cells during tumor progression, it was found that NKG2D can control the fate and TOX expression of tumor-reacting CD8(+) T cells.
Review
Oncology
Chaofeng Liang, Shuxin Huang, Yujie Zhao, Shaohua Chen, Yangqiu Li
Summary: TOX is a transcriptional factor containing the highly conserved HMG-box region, involved in maintaining tumors and promoting T cell exhaustion. It plays an important role in lymphocytic malignancies and may serve as a potential immune biomarker and target in immunotherapy for hematological malignancies.
BIOMARKER RESEARCH
(2021)
Article
Rheumatology
Suying Liu, Yanlei Yang, Liuting Zeng, Li Wang, Chengmei He, Zhilei Chen, Jinlei Sun, Taibiao Lyu, Mu Wang, Hua Chen, Fengchun Zhang
Summary: This study revealed the dysregulation and underlying mechanism of naive CD4(+) T cells in primary SS. The upregulation of TOX in pSS naive CD4(+) T cells promoted Tfh cell differentiation, and the IFN-alpha-JAK-STAT1 signaling pathway and TOX may serve as potential therapeutic targets for pSS.
Article
Medicine, Research & Experimental
Leonard Mvaya, Trevor Khaba, Agness E. Lakudzala, Thandeka Nkosi, Ndaru Jambo, Innocent Kadwala, Anstead Kankwatira, Priyanka D. Patel, Melita A. Gordon, Tonney S. Nyirenda, Kondwani C. Jambo, Zaza M. Ndhlovu
Summary: The duodenum serves as a major site of HIV persistence during suppressive antiretroviral therapy, with tissue-resident memory (Trm) CD8+ T cells playing a significant role. HIV-specific CD8+ Trm cells in the duodenum are enriched and exhibit high polyfunctionality but lack expression of canonical cytolytic molecules. These findings shed light on the mechanisms of HIV persistence in the duodenum and have implications for cure therapies.
Article
Oncology
Ying Chen, Zhongxin Feng, Xingy Kuang, Peng Zhao, Bingqing Chen, Qin Fang, Weiwei Cheng, Jishi Wang
Summary: The study highlights the role of lactate in tumor progression and T cell dysfunction in AML patients. It shows that targeting lactate could be a potential precision therapeutic strategy for AML patients and suggests lactate as a predictive biomarker for patient response to antitumor therapies. Additionally, the study reveals the correlation between lactate levels and CD8(+) T cell function, providing insights into the mechanisms underlying T cell dysfunction in AML.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Zahra Maria, Emma Turner, Agnieshka Agasing, Gaurav Kumar, Robert C. Axtell
Summary: The study showed that pertussis toxin (PTX) significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells and promoting the accumulation of B cells in the central nervous system. The data suggest that PTX inhibits the migration of pathogenic Th17 cells while promoting the accumulation of pathogenic B cells during Th17-EAE, providing useful information for adoptive-transfer Th17-EAE and studying the pathogenic mechanisms of B cells in multiple sclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Arjun Kharel, Jian Shen, Ryan Brown, Yao Chen, Christine Nguyen, Donia Alson, Theresa Bluemn, Jie Fan, Kexin Gai, Bin Zhang, Matthew Kudek, Nan Zhu, Weiguo Cui
Summary: During chronic viral infection and cancer, a subset of progenitor CD8+ T cells continuously gives rise to terminally exhausted cells and cytotoxic effector cells. The chromatin remodeling complex PBAF plays a role in maintaining chromatin accessibility of multiple genetic pathways and transcriptional programs to restrain proliferation and promote T cell exhaustion. Perturbation of PBAF complex constrained exhaustion and promoted expansion of tumor-specific CD8+ T cells, resulting in antitumor immunity and implicating PBAF as a potential target for cancer immunotherapy.
Article
Immunology
Raphael Kuhn, Ioana Sandu, Andreas Agrafiotis, Kai-Lin Hong, Danielle Shlesinger, Daniel Neimeier, Doron Merkler, Annette Oxenius, Sai T. Reddy, Alexander Yermanos
Summary: CD8+ T cells play a crucial role in viral infections and exhibit diverse phenotypes and effector functions. By analyzing the TCR repertoire and transcriptome of virus-specific CD8 T cells in murine models, we identified infection-specific populations corresponding to different phenotypes. Chronic and latent infections resulted in a higher proportion of clonally expanded T cells compared to acute infection. We also observed a relationship between transcriptional heterogeneity and clonal expansion.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Andreas Agrafiotis, Raphael Dizerens, Ilena Vincenti, Ingrid Wagner, Raphael Kuhn, Danielle Shlesinger, Marcos Manero-Carranza, Tudor-Stefan Cotet, Kai-Lin Hong, Nicolas Page, Nicolas Fonta, Ghazal Shammas, Alexandre Mariotte, Margot Piccinno, Mario Kreutzfeldt, Benedikt Gruntz, Roy Ehling, Alessandro Genovese, Alessandro Pedrioli, Andreas Dounas, Soeren Franzenburg, Hayrettin Tumani, Tania Kuempfel, Vladyslav Kavaka, Lisa Ann Gerdes, Klaus Dornmair, Eduardo Beltran, Annette Oxenius, Sai T. T. Reddy, Doron Merkler, Alexander Yermanos
Summary: B cells play a role in the development of inflammatory diseases in the central nervous system (CNS) through various mechanisms. In this study, B cells from murine models of viral infections and autoimmunity in the CNS were profiled. It was found that there is a population of clonally expanded, antibody-secreting cells that respond to viral antigens and persist in the brain even after infection is resolved. Similar populations were also detected in relapsing multiple sclerosis patients.
ACTA NEUROPATHOLOGICA
(2023)
Article
Biochemistry & Molecular Biology
Florian Ruiz, Benjamin Peter, Jessica Rebeaud, Solenne Vigne, Valentine Bressoud, Martin Roumain, Tania Wyss, Yannick Yersin, Ingrid Wagner, Mario Kreutzfeldt, Marisa Pimentel Mendes, Camille Kowalski, Gael Boivin, Leonard Roth, Markus Schwaninger, Doron Merkler, Giulio G. Muccioli, Stephanie Hugues, Tatiana Petrova, Caroline Pot
Summary: The vasculature plays a critical role in regulating leukocyte trafficking into the central nervous system (CNS) during inflammatory diseases such as multiple sclerosis (MS). However, the impact of endothelial-derived factors on CNS immune responses is still unclear. This study investigates the role of Cholesterol-25-hydroxylase (Ch25h)-derived bioactive lipids in promoting neuroinflammation and reveals that Ch25h deficiency in CNS endothelial cells attenuates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.
Article
Multidisciplinary Sciences
Andrew G. Soerens, Marco Kunzli, Clare F. Quarnstrom, Milcah C. Scott, Lee Swanson, J. J. Locquiao, Hazem E. Ghoneim, Dietmar Zehn, Benjamin Youngblood, Vaiva Vezys, David Masopust
Summary: This study explored the long-term response of mouse T cells to repeated immunizations and found that these cells retained the ability to respond to vaccines, proliferate, perform antimicrobial functions, and form quiescent memory cells. These findings provide insights into memory cell differentiation, exhaustion, cancer, and aging.
Editorial Material
Immunology
Anna M. Schulz, Caitlin C. Zebley, Ben Youngblood, Dietmar Zehn
Article
Immunology
Anna-Friederike Marx, Sandra M. Kallert, Tobias M. Brunner, Jose A. Villegas, Florian Geier, Jonas Fixemer, Tiago Abreu-Mota, Peter Reuther, Weldy V. Bonilla, Jelizaveta Fadejeva, Mario Kreutzfeldt, Ingrid Wagner, Patricia Aparicio-Domingo, Leo Scarpellino, Melanie Charmoy, Daniel T. Utzschneider, Claudia Hagedorn, Min Lu, Karen Cornille, Karsten Stauffer, Florian Kreppel, Doron Merkler, Dietmar Zehn, Werner Held, Sanjiv A. Luther, Max Loehning, Daniel D. Pinschewer
Summary: This study shows that T cell factor 1 (Tcf-1) expressing CD8+ T cells, known as stem-like CD8+ T cells (CD8+SL), play a crucial role in immune defense against chronic viral infection and cancer. It identifies interleukin-33 (IL-33) as a pivotal factor for the expansion and functioning of CD8+SL and virus control.
Article
Immunology
Stefanie Scherer, Susanne G. Oberle, Kristiyan Kanev, Ann-Katrin Gerullis, Ming Wu, Gustavo P. de Almeida, Daniel J. Puleston, Francesc Baixauli, Lilian Aly, Alessandro Greco, Tamar Nizharadze, Nils B. Becker, Madlaina V. Hoesslin, Lara V. Donhauser, Jacqueline Berner, Talyn Chu, Hayley A. McNamara, Zeynep Esencan, Patrick Roelli, Christine Wurmser, Ingo Kleiter, Maria J. G. T. Vehreschild, Christoph A. Mayer, Percy Knolle, Martin Klingenspor, Valeria Fumagalli, Matteo Iannacone, Martin Prlic, Thomas Korn, Erika L. Pearce, Thomas Hoefer, Anna M. Schulz, Dietmar Zehn
Summary: The study shows that dihydroorotate dehydrogenase in the de novo pyrimidine synthesis pathway functions as a cell fate checkpoint that allows for targeted reduction of effector T cells without affecting memory T cells. Blocking pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase is effective in treating autoimmunity and preventing expansion of rapidly dividing cell populations. Early effector T cells are more susceptible to pyrimidine starvation due to their higher proliferative rate and lower pyrimidine synthesis capacity compared to memory T cell precursors. This cell fate checkpoint can potentially lead to new methods for manipulating effector T cell responses.
Article
Immunology
Diego von Werdt, Bilgi Gungor, Juliana Barreto de Albuquerque, Thomas Gruber, Daniel Zysset, Cheong K. C. Kwong Chung, Antonia Correa-Ferreira, Regina Berchtold, Nicolas Page, Mirjam Schenk, John H. Kehrl, Doron Merkler, Beat A. Imhof, Jens V. Stein, Jun Abe, Gleb Turchinovich, Daniela Finke, Adrian C. Hayday, Nadia Corazza, Christoph Mueller
Summary: Members of the Regulator of G-protein signaling (Rgs) family regulate G protein signaling by increasing the GTPase activity of G alpha protein subunits. Rgs1, a member of the Rgs family, preferentially deactivates G alpha q and G alpha i subunits, attenuating chemokine receptor-mediated immune cell trafficking. Its impact on tissue-resident T cells and immunosurveillance in barrier tissues is not fully understood.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yanyin Xu, Jiasheng Zhang, Heon-Woo Lee, Guogang Zhang, Yongping Bai, Michael Simons
Summary: Understanding the development of cerebral vasculature is crucial for CNS research and therapeutics. A new method called flattened cortex whole mount (FCWM) technique was developed for high-resolution imaging of pial cerebral vessels. FCWM offers advantages such as precise localization of blood vessels and compatibility with confocal imaging. Application of FCWM revealed type-specific maturation and remodeling of cerebral blood vessels linked to endothelial proliferation, during postnatal development and stroke settings.
Editorial Material
Immunology
Jacqueline Berner, Dietmar Zehn
Summary: Beta-blockers, traditionally used for treating cardiovascular diseases, have been found to enhance the effectiveness of immunotherapy against tumors and chronic infections.
Editorial Material
Clinical Neurology
Tristan Born, Paola Vassallo, Dela Golshayan, Giovanni Di Liberto, Jean-Philippe Brouland, Kristof Egervari, Doron Merkler, Renaud A. Du Pasquier, Raphael Bernard-Valnet
Summary: This article reports a case of a kidney transplant recipient developing PML and receiving recombinant human interleukin 7 for immune responses against JCV. The article provides an overview of the immune mechanisms underlying PML development and immune restoration within the CNS after JCV infection. Immunotherapeutic strategies based on current understanding of the disease hold promise in managing PML patients.
Article
Oncology
Lara Victoria Donhauser, Julia Veloso de Oliveira, Cordula Schick, Wenzel Manlik, Sabrina Styblova, Sarah Lutzenberger, Michael Aigner, Patrick Philipp, Sebastian Robert, Beate Gandorfer, Dirk Hempel, Louisa Hempel, Dietmar Zehn
Summary: The study analyzed the response to BioNTech/Pfizer's anti-SARS-CoV-2 mRNA vaccine in 237 oncology outpatients and found that patients should wait at least 6 months to 12 months after systemic therapy before receiving mRNA vaccination.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Endocrinology & Metabolism
Yi-Heng Tai, Daniel Engels, Giuseppe Locatelli, Ioanna Emmanouilidis, Caroline Fecher, Delphine Theodorou, Stephan A. Mueller, Simon Licht-Mayer, Mario Kreutzfeldt, Ingrid Wagner, Natalia Prudente de Mello, Sofia-Natsouko Gkotzamani, Laura Trovo, Arek Kendirli, Almir Aljovic, Michael O. Breckwoldt, Ronald Naumann, Florence M. Bareyre, Fabiana Perocchi, Don Mahad, Doron Merkler, Stefan F. Lichtenthaler, Martin Kerschensteiner, Thomas Misgeld
Summary: In this study, the authors investigate the metabolic and bioenergetic responses in axonal compartments during multiple sclerosis (MS). They demonstrate that upregulating the tricarboxylic acid cycle can protect against energy deprivation induced by neuroinflammation. The researchers use cell-type-specific mitochondrial proteomics and in vivo biosensor imaging to analyze how inflammation alters the molecular composition and function of neuronal mitochondria, finding that neuroinflammatory lesions lead to widespread axonal ATP deficiency and impaired electron transport chain function.
Article
Physiology
Michael Simons
Summary: Endothelial-to-mesenchymal transition (EndMT) is a physiological process that plays important roles in both embryonic development and adult tissue pathology. Recent research has revealed a complex set of interactions underlying EndMT, which contributes to the pathophysiological basis of various deadly and intractable diseases. This mini review aims to summarize the recent advances and provide a comprehensive perspective on this complex field.
CURRENT OPINION IN PHYSIOLOGY
(2023)
