Review
Biochemistry & Molecular Biology
Jian Lu, Jing Wu, Xueli Xia, Huiyong Peng, Shengjun Wang
Summary: RA is a chronic autoimmune disease characterized by joint and systemic inflammation, with Tfh cells playing a crucial role in the pathogenesis of the disease and affecting disease activity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Immunology
Xindi Wei, Xiaoyin Niu
Summary: Tfh cells, a new subset of CD4+ T cells, mainly express CXCR5 and ICOS surface molecules, secrete IL-21, and require BCL-6 transcription factor. They exist in germinal centers (GCs) of lymphoid organs and peripheral blood, playing critical roles in B cell development, GC formation, and antibody production. Aberrant proliferation and function of Tfh cells contribute to autoimmune diseases, and they can potentially be used as therapeutic targets.
JOURNAL OF AUTOIMMUNITY
(2023)
Review
Immunology
Nengqi Lin, Wei Yin, Heather Miller, Maria G. Byazrova, Andres A. Herrada, Kamel Benlagha, Pamela Lee, Fei Guan, Jiahui Lei, Quan Gong, Youqing Yan, Alexander Filatov, Chaohong Liu
Summary: Hepatitis B has become a major health threat worldwide, particularly in developing countries and regions. Infection with hepatitis B virus significantly increases the risk of liver diseases such as cirrhosis and cancer. The immune response against hepatitis B is mainly regulated by CD8+ T cells, which play a key role in fighting viral infections, while regulatory T cells prevent excessive immune response. Additionally, follicular T helper cells have a critical role in B-cell activation, proliferation, differentiation, and the formation of germinal centers. The development of hepatitis B virus is generally associated with immune system disorders or dysfunctions. This review focuses on the important functions and biological processes of regulatory T cells and follicular T helper cells during HBV infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Bradley Salvatore, Rachel S. Resop, Brent R. Gordon, Marta Epeldegui, Otoniel Martinez-Maza, Begona Comin-Anduix, Alex Lam, Ting-Ting Wu, Christel H. Uittenbogaart
Summary: Humoral immune response plays a crucial role in combating pathogens by producing specific antibodies. T follicular helper (TFH) cells contribute to both B-cell antibody production and HIV persistence. T follicular regulatory (TFR) cells, which suppress TFH cell function, exhibit similar surface markers. The increase in TFH cells observed in HIV infection may partially be due to an increase in TFR cells. Using multicolor flow cytometry, we identified peripheral blood TFH (pTFH) and peripheral blood TFR (pTFR) cells and found that the frequency of pTFH cells was higher in HIV-infected individuals. Additionally, pTFH cells expressed lower levels of CCR5, a key factor in HIV persistence. The constitutive expression of CCR5 in TFR cells indicates their potential contribution to HIV persistence.
Article
Rheumatology
Qinglian Jiang, Jiakai Wang, Hongkun Jiang, Wei Li, Yini Sun, Yu Shan, Tong Wei, Xuyang Chi, Shihan Yu, Xiaoxue Ma
Summary: This study found that Tph cells are increased in SLE patients and are strongly associated with disease activity and renal involvement. The synergy of IFN-alpha and IL-2 increases Tph cells through competitive transcriptional regulation, which could be one of the mechanisms responsible for pathological formation of ELSs.
Article
Immunology
Matthew T. T. Ollerton, Joy M. M. Folkvord, Andriana La Mantia, David A. A. Parry, Amie L. L. Meditz, Martin D. D. McCarter, Richard T. D'Aquila, Elizabeth Connick
Summary: Follicular helper CD4(+) T cells (TFH) are major sites of HIV replication, but follicular regulatory CD4(+) T cells (TFR) limit HIV replication by suppressing TFH through IL-2 restriction. TFR reduce TFH viability and HIV infected TFH, and IL-2 enhances TFH viability but decreases HIV replication in the presence of TFR.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Hiroyuki Yoshitomi, Hideki Ueno
Summary: The interactions between CD4(+)T cells and B cells are crucial for antibody responses and autoimmune diseases. Recent studies identified a new subset of CD4(+)B helper T cells called peripheral helper T (Tph) cells, which provide help to B cells in inflamed tissues and share some functions with Tfh cells.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Immunology
Xiaoxue Ma, Shingo Nakayamada
Summary: T follicular helper (Tfh) cells participate in humoral immune responses by promoting inflammation and aiding B cells survival, proliferation, maturation, and generation of autoantibodies. The plasticity of Tfh cells allows for adjustment of differentiation direction based on immune response level, regulated by various signaling factors such as cytokines, receptors, transcription factors, and genes. The STAT family signaling pathways play a crucial role in Tfh formation, with each member contributing to Tfh differentiation through mutual restraint and cooperation among cytokine-STAT signals.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Fabienne Burger, Kapka Miteva, Daniela Baptista, Aline Roth, Rodrigo A. Fraga-Silva, Catherine Martel, Nikolaos Stergiopulos, Francois Mach, Karim J. Brandt
Summary: The study shows that follicular regulatory helper T cells (T-FR) can control regulatory B cell (B-REG) populations in mice models on a high-cholesterol diet, leading to the suppression of proatherogenic processes. This suggests that T-FR cells may have atheroprotective effects by modulating immune processes related to atherosclerosis.
CARDIOVASCULAR RESEARCH
(2021)
Article
Critical Care Medicine
Laura Bauer, Lisa Jasmin Mueller, Sarah M. Volkers, Frederik Heinrich, Mir-Farzin Mashreghi, Clemens Ruppert, Leif E. Sander, Andreas Hutloff
Summary: Pulmonary sarcoidosis is driven not only by T-helper type 1 cells and macrophages, but also by T follicular helper-like cells and germinal center-like reactions in the inflamed lung tissue. This new pathomechanism of active T-cell/B-cell cooperation and local production of potentially pathogenic antibodies should be taken into consideration for diagnosis and treatment.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Review
Immunology
Jingjing Qi, Chang Liu, Ziran Bai, Xia Li, Genhong Yao
Summary: Tfh cells and Tfr cells play crucial roles in the pathogenesis of autoimmune diseases, regulating B cell differentiation and antibody production by expressing specific surface markers and cytokines. Understanding the phenotype, differentiation, and function of these cells may provide insight into potential therapies targeting the balance of Tfh and Tfr cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pathology
Yoshiaki Kobayashi, Nozomu Kurose, Xin Guo, Akihiro Shioya, Morimasa Kitamura, Hiroyuki Tsuji, Sohsuke Yamada
Summary: This study investigated the immune responses and relationship between Tfh and Th1 cells in patients with Warthin tumours, finding that Tfh were involved in the formation and maintenance of lymphoid follicles in WTs. The cyst-type tumours exhibited more T-bet positive lymphocytes, suggesting a Th1-dominant cellular immune response causing damage to tumour tissue.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Immunology
Kalliopi Ioannidou, Daba-Rokhya Ndiaye, Alessandra Noto, Craig Fenwick, Sotirios P. Fortis, Giuseppe Pantaleo, Constantinos Petrovas, Laurence de Leval
Summary: This study utilized a quantitative multiplexed immunofluorescence approach to comprehensively characterize Tfh cells in human tonsils and lymph nodes. Different subsets of Tfh cells were identified at tissue level based on differential expression of surface receptors and nuclear factors. Moreover, significant differences in Tfh cell profile signatures between health and disease were revealed.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Yuwen Chen, Liping Luo, Yongzhi Zheng, Qiaoyun Zheng, Na Zhang, Donghui Gan, Shimuye Kalayu Yirga, Zhenxing Lin, Qizhen Shi, Lin Fu, Jianda Hu, Yingyu Chen
Summary: This study aimed to clarify the roles of platelet desialylation and circulating TFHs in patients with immune thrombocytopenia (ITP) and non-ITP thrombocytopenia. The findings suggest that platelet desialylation and circulating TFHs may become potential biomarkers for evaluating the disease process associated with thrombocytopenia in patients with ITP and non-ITP.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Guangli Gu, Xiaodan Lv, Gengfeng Liu, Ruizhi Zeng, Shiquan Li, Lan Chen, Zhaoliang Liang, Huiqin Wang, Fei Lu, Lingling Zhan, Xiaoping Lv
Summary: The study found that Tnfaip6 secreted by BM-MSCs can alleviate IBD by inhibiting Tfh differentiation, promoting Tfr differentiation, and improving the imbalance of Tfh/Tfr in mice.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lahiru Gangoda, Robyn L. Schenk, Sarah A. Best, Christina Nedeva, Cynthia Louis, Damian B. D'Silva, Kirsten Fairfax, Andrew G. Jarnicki, Hamsa Puthalakath, Kate D. Sutherland, Andreas Strasser, Marco J. Herold
Summary: Inflammation is a natural defense mechanism of the body against pathogens, but its sustained presence can lead to various pathologies. The excessive activity of immune cells plays a critical role in chronic inflammation, but research suggests that A1 may not have a major impact on the survival of immune cells during inflammation.
CELL DEATH AND DIFFERENTIATION
(2022)
Correction
Biochemical Research Methods
Fengyuan Hu, Jia Lu, Louise S. Matheson, Manuel D. Diaz-Munoz, Alexander Saveliev, Martin Turner
Article
Multidisciplinary Sciences
Seyhan Yazar, Jose Alquicira-Hernandez, Kristof Wing, Anne Senabouth, M. Grace Gordon, Stacey Andersen, Qinyi Lu, Antonia Rowson, Thomas R. P. Taylor, Linda Clarke, Katia Maccora, Christine Chen, Anthony L. Cook, Chun Jimmie Ye, Kirsten A. Fairfax, Alex W. Hewitt, Joseph E. Powell
Summary: This study utilizes single-cell RNA sequencing to uncover the genetic drivers of interindividual variation in the human immune system. The researchers identify specific loci that have cell type-specific effects on gene expression and demonstrate dynamic allelic effects in B cells. Additionally, they use Mendelian randomization to determine the causal route by which risk loci contribute to autoimmune disease at the cellular level.
Article
Multidisciplinary Sciences
Georg Petkau, Twm J. Mitchell, Krishnendu Chakraborty, Sarah E. Bell, Vanessa D. Angeli, Louise Matheson, David J. Turner, Alexander Saveliev, Ozge Gizlenci, Fiamma Salerno, Peter D. Katsikis, Martin Turner
Summary: RNA binding proteins ZFP36 and ZFP36L1 limit the rate of differentiation and the potency of activated CD8(+) T cells by directly binding mRNA of transcription factors and cytokines, enforcing dependency on costimulation for full T cell activation and effector differentiation.
NATURE COMMUNICATIONS
(2022)
Article
Biology
David J. Turner, Alexander Saveliev, Fiamma Salerno, Louise S. Matheson, Michael Screen, Hannah Lawson, David Wotherspoon, Kamil R. Kranc, Martin Turner
Summary: In this study, we used a CRISPR/Cas9 knockout screen to identify the roles of RNA binding proteins (RBPs) in the differentiation and survival of antibody secreting plasma cells. Through this screen, we discovered that CSDE1, STRAP, and YTHDF2 promote the accumulation of CD138 + cells, while EIF3K, EIF3L, and components of the CCR4-NOT complex inhibit CD138 + cell accumulation. Additionally, YTHDF2-deficient plasma cells were found to fail in accumulation in chimeric mouse models.
Article
Cell Biology
Pin Shie Quah, Vivien Sutton, Eden Whitlock, William A. Figgett, Daniel M. Andrews, Kirsten A. Fairfax, Fabienne Mackay
Summary: The role of B-cell-activating factor (BAFF) in the homeostasis of natural killer (NK) cells has been studied. BAFF signaling through BAFF receptor is essential for sustaining NK cell numbers in the spleen, but BAFF is dispensable for NK cell maturation. NK cells from BAFF deficient and BAFF transgenic mice showed similar interferon-gamma production and tumor cell killing capacity compared to wild-type mice. NK cells do not express BAFF receptors in the steady state or in a SLE mouse model.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Louise S. Matheson, Georg Petkau, Beatriz Saenz-Narciso, Vanessa D'Angeli, Jessica McHugh, Rebecca Newman, Haydn Munford, James West, Krishnendu Chakraborty, Jennie Roberts, Sebastian Lukasiak, Manuel D. Diaz-Munoz, Sarah E. Bell, Sarah Dimeloe, Martin Turner
Summary: The ZFP36 family of RNA-binding proteins directly limit gene expression to repress metabolism and differentiation in CD4(+) T cells, specifically targeting transcription factors and transcripts encoding rate-limiting enzymes. Deficiency of ZFP36 and ZFP36L1 result in increased cellular glutamine content and activation of anabolic processes. Glutamine and alpha-ketoglutarate may serve as limiting factors for the acquisition of cytotoxic CD4(+) T cell fate.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Ines C. Osma-Garcia, Dunja Capitan-Sobrino, Mailys Mouysset, Yann Aubert, Orlane Maloudi, Martin Turner, Manuel D. Diaz-Munoz
Summary: This study reveals the importance of tight regulation of RNA splicing by TIA1 and TIAL1 for the expression of integrative transcriptional programs that control DNA damage sensing and repair during B cell development.
Review
Biochemistry & Molecular Biology
Martin Turner
Summary: Pre-existing but untranslated or 'poised' mRNA serves as a rapid response mechanism and a safeguard in immune cells. The molecular mechanisms that control the translation of poised mRNA have yet to be fully understood, but they likely involve intrinsic properties of the mRNA and its interactions with trans-acting factors. This article discusses potential regulatory mechanisms.
Review
Genetics & Heredity
Jennifer Lim, Venessa Chin, Kirsten Fairfax, Catia Moutinho, Dan Suan, Hanlee Ji, Joseph E. Powell
Summary: Genomics has been widely used in clinical practice, leading to innovations in genetic screening, rare disease diagnosis, and molecularly guided therapy choice. Single-cell technologies have the potential to revolutionize genomic medicine by unveiling the cellular heterogeneity underlying disease pathology and mechanisms. However, challenges in translating single-cell genomics from research to clinical practice need to be addressed.
NATURE REVIEWS GENETICS
(2023)
Article
Cell Biology
Andrew C. Cicchetto, Elsie C. Jacobson, Hannah Sunshine, Blake R. Wilde, Abigail S. Krall, Kelsey E. Jarrett, Leslie Sedgeman, Martin Turner, Kathrin Plath, M. Luisa Iruela-Arispe, Thomas Q. de Aguiar Vallim, Heather R. Christofk
Summary: Cellular metabolism is regulated by growth factor signaling, and this study identifies the ZFP36/L1/L2 family of RNA-binding proteins and mRNA decay factors as key regulators of metabolic rewiring downstream of acute growth factor signaling. The researchers found that ZFP36 directly promotes the degradation of multiple metabolic enzyme and nutrient transporter mRNAs, including those encoding rate-limiting steps in metabolic pathways. They also demonstrated that ZFP36-mediated mRNA decay affects the expression and activity of Enolase 2 (Eno2), and plays a role in VEGF-stimulated developmental retinal angiogenesis.
Article
Biology
Ana Martinez-Riano, Pilar Delgado, Rut Tercero, Sara Barrero, Pilar Mendoza, Clara L. L. Oeste, David Abia, Elena Rodriguez-Bovolenta, Martin Turner, Balbino Alarcon
Summary: Researchers have developed an antigen-specific in vitro germinal center system using just two cell types, B cells and CD4+ T cells, to investigate the immune response and T cell help in the production of class-switched high affinity immunoglobulins. The lack of an antigen-specific in vitro germinal center system has been a major obstacle in understanding the mechanisms of B cell:T cell cooperation. By using this system, the researchers demonstrated that T cells provide directional help to antigen-presenting B cells, but not bystander B cells, leading to the generation of class-switched antibodies.
COMMUNICATIONS BIOLOGY
(2023)
Review
Cell & Tissue Engineering
Ariel Simpson, Alex W. Hewitt, Kirsten A. Fairfax
Summary: This review outlines strategies and safety mechanisms for generating "universal" cell donor lines to reduce wait time, eliminate immune rejection risk, and improve treatment efficacy in transplantation medicine.
Review
Genetics & Heredity
Niles Nelson, Simone Feurstein, Aram Niaz, Jia Truong, Jessica K. Holien, Sionne Lucas, Kirsten Fairfax, Joanne Dickinson, Tracy M. Bryan
Summary: The purpose of this study is to improve the genomic diagnosis of patients with underlying telomere biology disorders (TBD) by reducing variants of uncertain significance through the application of functional genomic evidence. The findings suggest a need for further assay standardization and assessment of benign variants to optimize the use of the PS3/BS3 criterion for TBD gene variant classification.
GENETICS IN MEDICINE
(2023)
Meeting Abstract
Immunology
G. Petkau, T. J. Mitchell, K. Chakraborty, S. E. Bell, V. D'Angeli, L. Matheson, D. J. Turner, A. Saveliev, O. Gizlenci, F. Salerno, P. D. Katsikis, M. Turner
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
