Article
Immunology
Junichi Ishikawa, Akira Suto, Kazuya Abe, Yuki Hayashi, Kensuke Suga, Shigeru Tanaka, Takahiro Kageyama, Arifumi Iwata, Kazumasa Suzuki, Kotaro Suzuki, Hiroshi Nakajima
Summary: Murine IL-17-producing γδT (γδT17) cells consist of natural γδT17 (nγδT17) cells and inducible γδT17 cells. IL-21 is dispensable for the fetal thymic development of nγδT17 cells, but required for the peripheral maintenance of Vδ4(+)nγδT17 cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Marta Sanz, Brendan T. Mann, Paul L. Ryan, Alberto Bosque, Daniel J. Pennington, Holger Hackstein, Natalia Soriano-Sarabia
Summary: Under non-pathological conditions, human ?d T cells represent a small fraction of CD3(+) T cells in peripheral blood (1-10%). They constitute a unique subset of T lymphocytes that recognize stress ligands or non-peptide antigens through MHC-independent presentation. Major human ?d T cell subsets, Vd1 and Vd2, expand in response to microbial infection or malignancy, but possess distinct tissue localization, antigen recognition, and effector responses. By comparing highly purified Vd1 and Vd2 cells, this study found distinct genetic and phenotypic signatures that define functional differences in ?d T cell populations, suggesting that Vd1 and Vd2 T cells are different lineages. These findings will facilitate further investigation into the ligand specificity and unique role of Vd1 and Vd2 cells in early immune responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sara Scaramuzzino, Delphine Potier, Robin Ordioni, Pierre Grenot, Dominique Payet-Bornet, Herve Luche, Bernard Malissen
Summary: The study demonstrated that γδ T-cell lineage development not only relies on the signaling of γδ TCR but also requires the regulatory role of LAT in mice lacking LAT expression.
Article
Immunology
Seungyoul Oh, Xin Liu, Sara Tomei, Mengxiao Luo, Jarrod P. Skinner, Stuart P. Berzins, Shalin H. Naik, Daniel H. D. Gray, Mark M. W. Chong
Summary: The alpha beta and gamma delta T cell lineages originate from common progenitors in the thymus. The earliest stage of T cell development, known as DN1, is a heterogeneous mixture of cells. Recent studies have shown that some gamma delta T cells may be derived from a subset of DN thymocytes that do not express CD117. These findings suggest that T cell development is more complex than previously thought. To better understand this process, researchers performed single cell RNA sequencing of mouse DN and gamma delta thymocytes and found that different DN stages comprise transcriptionally diverse subpopulations of cells. They also discovered that specific subpopulations of DN1 thymocytes exhibit preferential development towards the gamma delta lineage, with some subpopulations producing IL-17 and others producing IFN gamma.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Guanyu Qu, Shengli Wang, Zhenlong Zhou, Dawei Jiang, Aihua Liao, Jing Luo
Summary: This article summarizes the current knowledge of the γδT cell phenotype in various tissues in mice and humans, describing the similarities and differences of tissue-resident γδT cells in these two species.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Jie Lv, Mengyao Han, Guangyu Liu, Wei Zhuang, Chun Wang, Ling Xie, Kaidireya Saimaier, Sanxing Han, Changjie Shi, Qiuhong Hua, Ru Zhang, Changsheng Du
Summary: Apoptosis is important in maintaining the homeostasis of the body and immune system, but its dysfunction can lead to autoimmune diseases like multiple sclerosis (MS). An animal model, experimental autoimmune encephalomyelitis (EAE), is used to study MS. In this study, we found that carboplatin (CA), a platinum anti-tumor drug, reduced inflammation and demyelination in EAE mice. CA also decreased pathogenic T cell numbers and proportions in the spleen and lymph nodes of EAE mice. Additionally, CA induced apoptosis and inhibited T cell proliferation. These findings suggest that CA has potential as a novel drug for MS treatment.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Yingying Wei, Zachary Braunstein, Jun Chen, Xinwen Min, Handong Yang, Lihua Duan, Lingli Dong, Jixin Zhong
Summary: Multiple sclerosis (MS) is an autoimmune disease mediated by T cells, but the exact signaling pathways involved in effector T cells in MS are not well understood. This study investigated the role of Janus kinase 2 (JAK2) and its potential as a therapeutic target in MS. The results showed that knockout of JAK2 in T cells prevented the development of MS in mice. In vitro experiments also demonstrated that JAK2 disruption suppressed the differentiation of TH1 cells and the production of IFN gamma. These findings suggest that overactive JAK2 signaling in T lymphocytes plays a critical role in MS and could be targeted for therapeutic intervention.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Chun Zhang, Xiuxing Liu, Jing Xiao, Fanwen Jiang, Luzhong Fa, Hui Jiang, Lin Zhou, Wenru Su, Zhuping Xu
Summary: Autoimmune uveitis is a non-infectious, inflammatory intraocular disease that affects the uveal and adjacent tissues, leading to visual loss. Activated γδ T cells play a significant role in the development of autoimmune uveitis by secreting pro-inflammatory factors and promoting Th17 cell responses. Understanding the mechanisms of γδ T cell involvement in different activation and disease states provides insights for the development of immunotherapies for treating autoimmune uveitis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Immunology
Lea Rimailho, Carla Faria, Marcin Domagala, Camille Laurent, Christine Bezombes, Mary Poupot
Summary: Despite advancements in therapy and increased survival rates, B cell malignancies often lead to relapse. Immune cell-based therapies, particularly γδ T cells, show promising results for cancer immunotherapy. Manipulating γδ T cells through immunotherapeutic approaches provides potential treatment strategies for B cell malignancies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Saisai Ren, Xiaorong Zhang, Hongbing Guan, Lihong Wu, Miao Yu, Dan Hou, Yongyong Yan, Xuechun Fang
Summary: The study found that the probiotic Lactobacillus acidipiscis in the intestine can suppress the development of multiple sclerosis by inducing the generation of regulatory T cells. This helps to inhibit the progression of the disease and shows potential for treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Haishan Li, Yingying Zeng, Shunchang Luo, Zhenhua Li, Fang Huang, Zonghua Liu
Summary: Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system (CNS) that mainly affects young adults. CD4+ T cells play a significant role in the inflammatory processes of MS. Ferroptosis, a newly discovered form of programmed cell death, has been found to be associated with CD4+ T cells, but its impact on MS remains unclear.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Anatomy & Morphology
Guanhua Li, Lu Liu, Zhihua Yin, Zhizhong Ye, Nan Shen
Summary: Research identified glutamine metabolism as a critical regulator for IL-17 production in gamma delta T cells, with pharmaceutical blocking of glutamine impairing IL-17 production. Glutamine metabolism could be a potential target for the treatment of gamma delta T cell related diseases, with in vivo application of glutamine antagonist showing promise in alleviating disease progression.
Review
Biochemistry & Molecular Biology
Hui Shao, Henry J. Kaplan, Deming Sun
Summary: Autoimmune diseases caused by T cells can originate from either Th1 or Th17-type pathogenic T cells, but it is uncertain whether they are influenced by distinct pathogenic factors and whether treatments effective for Th1 responses work for Th17 responses. Through a systematic analysis in a mouse model of experimental autoimmune uveitis (EAU), it was found that these two pathogenic responses differ significantly in their pathological progressions and treatment susceptibility.
Article
Rheumatology
Celine Mortier, Eric Gracey, Julie Coudenys, Teddy Manuello, Tine Decruy, Margaux Maelegheer, Flore Stappers, Elisabeth Gilis, Djoere Gaublomme, Luc Van Hoorebeke, Sophie Van Welden, Catherine Ambler, Martin Hegen, Peter Symanowicz, Stefan Steyn, Gabriel Berstein, Dirk Elewaut, Koen Venken
Summary: Inhibiting ROR gamma t can effectively improve skin, joint, and gut inflammation in a preclinical PsA model, with reduction in clinical scores, weight loss, bone density, and surface erosions. ROR gamma t blockade also decreases IL-17 immune responses in PsA-affected tissues. Thus, targeting ROR gamma t may be a potential therapeutic approach for PsA.
Article
Pharmacology & Pharmacy
Katsunori Endo, Toko Sawa, Yuna Tanaka, Takeru Saiki, Hazuki Haga, Lana Rizeq, Haruka Aso, Momoka Isono, Fumie Niitsuma, Akihiro Masaki, Hidefumi Makabe, Sachi Tanaka
Summary: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system caused by overactivation of T cells. Procyanidins, polyphenols with anti-inflammatory properties, can inhibit cytokine production in T cells. In this study, the effects of Procyanidin B2 gallate (PCB2DG) on T cell-mediated autoimmune disease were investigated. The results showed that oral administration of PCB2DG significantly improved symptoms in a model of MS. This improvement was associated with the suppression of T cell-mediated cytokines and the infiltration of T cells in the spinal cord, suggesting that PCB2DG ameliorated spinal cord injury. The glycolytic activity of spleen cells was also analyzed, revealing that PCB2DG inhibited the increase in glycolysis observed during the development of MS.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Christopher Sie, Ravi Kant, Christian Peter, Andreas Muschaweckh, Monika Pfaller, Lucy Nirschl, Helena Dominguez Moreno, Tereza Chadimova, Gildas Lepennetier, Tanja Kuhlmann, Rupert Ollinger, Thomas Engleitner, Roland Rad, Thomas Korn
Summary: Th17 cells have an intrinsic feedback mechanism to control their pathogenicity, involving the production of IL-24 and secretion of IL-10. IL-24 interacts with Grim19 on the inner mitochondrial membrane to promote STAT3 accumulation in the mitochondrial compartment, which serves as a rheostat to regulate nuclear STAT3 activity. This mechanism plays an important role in restricting immunopathology associated with Th17 cells.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Clinical Neurology
Rachel C. Kenney, Mengling Liu, Lisena Hasanaj, Binu Joseph, Abdullah Abu Al-Hassan, Lisanne J. Balk, Raed Behbehani, Alexander Brandt, Peter A. Calabresi, Elliot Frohman, Teresa C. Frohman, Joachim Havla, Bernhard Hemmer, Hong Jiang, Benjamin Knier, Thomas Korn, Letizia Leocani, Elena Hernandez Martinez-Lapiscina, Athina Papadopoulou, Friedemann Paul, Axel Petzold, Marco Pisa, Pablo Villoslada, Hanna Zimmermann, Lorna E. Thorpe, Hiroshi Ishikawa, Joel S. Schuman, Gadi Wollstein, Yu Chen, Shiv Saidha, Steven Galetta, Laura J. Balcer
Summary: This study validates the use of intereye differences (IEDs) in peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell + inner plexiform (GCIPL) thickness by spectral domain optical coherence tomography (SD-OCT) for identifying people with a history of unilateral optic neuritis (ON). Machine learning classification and a composite score combining OCT and visual measures improve the diagnostic capability of SD-OCT for distinguishing people with multiple sclerosis (PwMS) from controls. GCIPL IED is the best discriminator of unilateral ON history among PwMS.
Article
Multidisciplinary Sciences
Meike Mitsdoerffer, Lilian Aly, Melanie Barz, Thomas Engleitner, Christopher Sie, Claire Delbridge, Gildas Lepennetier, Rupert Oellinger, Monika Pfaller, Benedikt Wiestler, Roland Rad, Bernhard Meyer, Benjamin Knier, Friederike Schmidt-Graf, Jens Gempt, Thomas Korn
Summary: Glioblastoma multiforme (GBM) shows resistance to immune responses, specifically to checkpoint inhibition. The study reveals that the brain tumor environment in GBM may cause infiltrating T helper cells to develop into type 17 T helper cells. The potential of targeting these CD4(+) TILs in the tumor-promoting milieu needs further investigation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Konstantin Lutz, Andrea Musumeci, Christopher Sie, Ezgi Dursun, Elena Winheim, Johannes Bagnoli, Christoph Ziegenhain, Lisa Rausch, Volker Bergen, Malte D. Luecken, Robert A. J. Oostendorp, Barbara U. Schraml, Fabian J. Theis, Wolfgang Enard, Thomas Korn, Anne B. Krug
Summary: This study investigates the heterogeneity and commitment of precursor cells in the mouse bone marrow that can differentiate into plasmacytoid and conventional dendritic cells (pDC and cDC). The authors identify a specific population of precursor cells expressing certain markers that can give rise to both pDCs and cDCs. They also show that type I interferon can regulate the balance between pDC and cDC production from these precursor cells. These findings shed light on the ontogeny and differentiation of dendritic cells.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Rachel Kenney, Mengling Liu, Lisena Hasanaj, Binu Joseph, Abdullah A. Al-Hassan, Lisanne Balk, Raed Behbehani, Alexander U. Brandt, Peter A. Calabresi, Elliot M. Frohman, Teresa Frohman, Joachim Havla, Bernhard Hemmer, Hong Jiang, Benjamin Knier, Thomas Korn, Letizia Leocani, Elena H. Martinez-Lapiscina, Athina Papadopoulou, Friedemann Paul, Axel Petzold, Marco Pisa, Pablo Villoslada, Hanna Zimmermann, Hiroshi Ishikawa, Joel S. Schuman, Gadi Wollstein, Yu Chen, Shiv Saidha, Lorna E. Thorpe, Steven L. Galetta, Laura J. Balcer
Summary: This study established normative values for pRNFL and GCIPL thicknesses using SD-OCT in healthy control subjects. It was found that after the age of 40 years, there was an accelerated decline in pRNFL and GCIPL thicknesses per decade, with no significant impact of sex or race/ethnicity on the thickness changes.
JOURNAL OF NEURO-OPHTHALMOLOGY
(2022)
Article
Clinical Neurology
Josephine Wauschkuhn, Gilberto Solorza Buenrostro, Lilian Aly, Susanna Asseyer, Rebecca Wicklein, Julia Maria Hartberger, Klemens Ruprecht, Mark Muehlau, Tanja Schmitz-Huebsch, Claudia Chien, Achim Berthele, Alexander U. U. Brandt, Thomas Korn, Friedemann Paul, Bernhard Hemmer, Hanna G. G. Zimmermann, Benjamin Knier
Summary: Thinning of retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by OCT is common in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event. The results showed that GCIP thickness measurement provides information for early risk stratification and progression of multiple sclerosis after the initial manifestation.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Immunology
Thomas Korn
Summary: Foxp3(+) regulatory T (Treg) cells play a crucial role in maintaining immune self-tolerance and confining autoimmune inflammation. They function differently in lymphoid and nonlymphoid tissues and can reside in nonlymphoid tissues for extended periods of time. These tissue-resident Treg cells are specialized to support immune functions and intrinsic functions of the tissues they reside in. This review focuses on the functional specialization of nonlymphoid tissue-resident Treg cells, particularly in the central nervous system, and discusses the challenges in utilizing their power for tissue homeostasis and regeneration.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
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
Multidisciplinary Sciences
Isabel J. Bauer, Ping Fang, Katrin F. Lammle, Sofia Tyystjarvi, Dominik Alterauge, Dirk Baumjohann, Hongsup Yoon, Thomas Korn, Hartmut Wekerle, Naoto Kawakami
Summary: This study explores the impact of microbiota on T cell activation and their role in triggering CNS inflammation using intravital imaging. The results show that microbiota stimulation in the small intestine leads to calcium signaling in T cells, which is microbiota and MHC class II dependent. This stimulation induces the expression of Th17-axis genes in encephalitogenic T cells and facilitates their migration into the CNS.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Dominic Bertram, Thanos Tsaktanis, Achim Berthele, Thomas Korn
Summary: Intrathecal synthesis of free light chains kappa (FLCK) is a reliable marker for differentiating inflammatory CNS pathologies, particularly autoimmune encephalitis (AIE), from non-inflammatory etiologies in subacute onset neuropsychiatric syndromes.
SCIENTIFIC REPORTS
(2023)
Meeting Abstract
Clinical Neurology
A. Afzali, L. Stuve, M. Pfaller, L. Aly, K. Steiger, B. Knier, T. Korn
MULTIPLE SCLEROSIS JOURNAL
(2022)
Meeting Abstract
Clinical Neurology
C. Noll, L. Aly, R. Wicklein, A. Berthele, C. Mardin, T. Korn, B. Hemmer, B. Knier
MULTIPLE SCLEROSIS JOURNAL
(2022)
Meeting Abstract
Clinical Neurology
E. F. Romahn, M. Bussas, T. Wiltgen, C. Noll, R. Wicklein, L. Aly, A. Berthele, C. Mardin, J. S. Kirschke, C. Zimmer, T. Korn, B. Hemmer, M. Muehlau, B. Knier
MULTIPLE SCLEROSIS JOURNAL
(2022)
Meeting Abstract
Clinical Neurology
J. Wauschkuhn, G. Solorza Buenrostro, L. Aly, S. Asseyer, R. Wicklein, J. M. Hartberger, K. Ruprecht, M. Muehlau, T. Schmitz-Huebsch, C. Chien, A. Berthele, A. U. Brandt, T. Korn, F. Paul, B. Hemmer, H. G. Zimmermann, B. Knier
MULTIPLE SCLEROSIS JOURNAL
(2022)
Meeting Abstract
Clinical Neurology
E. Wolf, R. Wicklein, L. Aly, C. Schmaderer, A. Berthele, C. Mardin, T. Korn, B. Hemmer, B. Hofauer, B. Knier
MULTIPLE SCLEROSIS JOURNAL
(2022)
