Review
Immunology
Mengdi Zhang, Xiaoxi Lin, Zhou Yang, Xia Li, Zhiguang Zhou, Paul E. Love, Jiaqi Huang, Bin Zhao
Summary: Cell metabolism plays a critical role in regulating T cell development, directing different metabolic pathways and signaling networks to match the specific functional requirements of different stages. Understanding this interplay may offer new therapeutic approaches to selectively regulate T cell subset functions and modulate autoimmunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Carolina Francelin, Luciana Peixoto Veneziani, Alessandro dos Santos Farias, Daniella Areas Mendes-da-Cruz, Wilson Savino
Summary: The thymus serves as a model for investigating the neuroimmune network, with neurotransmitters and receptors playing key roles in the regulation of thymocyte development and function. Numerous neurotransmitters of non-neuronal origin are produced within the thymus and are likely important players in T-cell development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Martijn Cordes, Karin Pike-Overzet, Erik B. B. Van Den Akker, Frank J. T. Staal, Kirsten Cante-Barrett
Summary: Flow cytometry has traditionally been used to characterize immune cells and their markers. Single-cell RNA-sequencing has revolutionized the study of immune development, allowing for the analysis of heterogenous tissues and the integration of omics data at the single-cell level. This integration contributes to our understanding of the immune system by revealing the heterogeneity within cell populations identified by surface markers and the correlation between RNA and protein data.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Immunology
Lifei Hou, Koichi Yuki
Summary: This study reveals the importance of CD11c in maintaining T cell survival by showing that CD11c deficiency leads to defects in T cell development in mice.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jessica Ruehle, Marco Ginzel, Stefanie Dietz, Julian Schwarz, Trim Lajqi, Sandra Beer-Hammer, Christian F. Poets, Christian Gille, Natascha Koestlin-Gille
Summary: Newborns, especially preterm infants, are more susceptible to infections due to their immature immune system. In particular, neonatal neutrophils have an immunomodulatory effect on T-cells. This study investigated the role of neonatal neutrophils in T-cell development in the thymus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Yu Gao, Ruining Liu, Chenfei He, Juan Basile, Mattias Vesterlund, Marie Wahren-Herlenius, Alexander Espinoza, Cassandra Hokka-Zakrisson, Fahad Zadjali, Akihiko Yoshimura, Mikael Karlsson, Berit Carow, Martin E. Rottenberg
Summary: SOCS3 is a critical regulator of immune responses and inflammation, with its expression in thymic stromal cells being essential for T cell development and maintenance of thymus architecture. The inhibition of SOCS3 led to impaired thymocyte differentiation, proliferation, and increased apoptosis at different cell stages, ultimately affecting the generation of recent thymic emigrants in peripheral organs. The interaction between SOCS3 in thymic epithelial cells and TRIM 21 had significant implications for thymic cellularity and gene expression related to T cell selection and lympho-stromal interactions.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Seungyoul Oh, Daniel H. D. Gray, Mark M. W. Chong
Summary: T cell development occurs in the thymus, where progenitors differentiate into a range of sublineages with distinct functions. By utilizing single-cell RNA sequencing approaches, researchers aim to gain unprecedented insight into the identity of cells and their gene expression programs, allowing for a deeper understanding of T cell development.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biology
Sayumi Fujimori, Izumi Ohigashi, Hayato Abe, Yosuke Matsushita, Toyomasa Katagiri, Makoto M. Taketo, Yousuke Takahama, Shinji Takada
Summary: The thymic epithelium plays a crucial role in supporting the development of T cells. This study found that enhanced expression of beta-catenin in thymic epithelial cells leads to thymic dysplasia and T cell deficiency in the embryonic period, while loss of beta-catenin function only slightly reduces cortical thymic epithelial cells and thymocytes in postnatal development.
Article
Neurosciences
Qianling Jiang, Xin Ma, Gaochen Zhu, Wen Si, Lingyu He, Guan Yang
Summary: This study investigated the effects of EAE induction on thymopoiesis and T cell development, revealing changes such as increased apoptosis, decreased proliferation, and a blockade in the transition from double-negative thymocytes to double-positive cells. It was also found that positive selection was disrupted in the thymus of EAE mice, along with an increased production of regulatory T cells.
EXPERIMENTAL NEUROLOGY
(2024)
Article
Immunology
Victoria Sun, Mark Sharpley, Karolina E. Kaczor-Urbanowicz, Patrick Chang, Amelie Montel-Hagen, Shawn Lopez, Alexandre Zampieri, Yuhua Zhu, Stephanie C. de Barros, Chintan Parekh, David Casero, Utpal Banerjee, Gay M. Crooks
Summary: Metabolic profiles of primary thymic and in vitro-derived mouse and human thymocytes were investigated using transcriptomics and extracellular flux analyses in this study. The study found that core metabolic pathways, such as glycolysis and oxidative phosphorylation, undergo dramatic changes during thymic T cell development, and in vitro T cell development mirrored the metabolic activity changes observed in primary thymus.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Emilie J. Cosway, Kieran D. James, Beth Lucas, Graham Anderson, Andrea J. White
Summary: Alpha beta T cells are essential components of effective immune responses, comprising subsets like CD4(+) helper cells, CD8(+) cytotoxic cells, and Foxp3(+) regulatory T cells. Their development in the thymus is crucial, with studies highlighting the critical role of the thymus medulla in shaping the peripheral T cell pool.
SEMINARS IN IMMUNOPATHOLOGY
(2021)
Article
Immunology
Kieran D. James, Andrea J. White, William E. Jenkinson, Graham Anderson
Summary: Gamma delta T-cell development and effector priming in adulthood are controlled by the medulla, with the medullary epithelial product CCL21 playing a crucial role in this process.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Cecile Apert, Ariel O. Galindo-Albarran, Sarah Castan, Claire Detraves, Heloise Michaud, Nicola McJannett, Bart Haegeman, Simon Fillatreau, Bernard Malissen, Georg Hollander, Saulius Zuklys, Jeremy C. Santamaria, Olivier P. Joffre, Paola Romagnoli, Joost P. M. van Meerwijk
Summary: This study reevaluated the role of IL-2 and IL-15 in the development of regulatory T-lymphocytes (Treg) and found that IL-2 and IL-15 play important non-redundant quantitative and qualitative roles in intrathymic Treg development.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Michele K. K. Anderson
Summary: Shifting levels of E proteins and Id factors are crucial in T cell commitment and differentiation, and understanding their roles and mechanisms can provide insights into the process of T cell development and differentiation. The Clutch model of differentiation describes how Id factors regulate E protein activity and chromatin remodeling to control T cell fate.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Takeshi Nitta, Hiroshi Takayanagi
Summary: The stromal microenvironment in the thymus is crucial for generating a functional T cell repertoire, with thymic epithelial cells (TECs) being the most prominent type. Besides TECs, other stromal cell types of mesenchymal origin also play important roles in controlling TEC development. The recently discovered functional effect of thymic fibroblasts on T cell repertoire selection is highlighted as a significant advancement in our understanding of thymic organogenesis and T cell development.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Cell Biology
Lizhen Wu, David G. Schatz
Article
Biochemistry & Molecular Biology
Soichi Hirokawa, Griffin Chure, Nathan M. Belliveau, Geoffrey A. Lovely, Michael Anaya, David G. Schatz, David Baltimore, Rob Phillips
NUCLEIC ACIDS RESEARCH
(2020)
Article
Genetics & Heredity
Eliza C. Martin, Celia Vicari, Louis Tsakou-Ngouafo, Pierre Pontarotti, Andrei J. Petrescu, David G. Schatz
Editorial Material
Immunology
Amy S. Weinmann, Ben A. Youngblood, Stephen T. Smale, Robert Brink, David G. Schatz, Michael McHeyzer-Williams
TRENDS IN IMMUNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Yuhang Zhang, Elizabeth Corbett, Shenping Wu, David G. Schatz
Article
Multidisciplinary Sciences
Yang Yang, Chang Liu, Wei Zhou, Wei Shi, Ming Chen, Baoyue Zhang, David G. Schatz, Yangbo Hu, Bin Liu
Summary: The MerR family of transcriptional regulators, such as EcmrR, activate promoters with a suboptimal structure for recognition by RNA polymerase holoenzyme. Structural insights into the EcmrR-dependent transcription process elucidate the mechanisms enabling optimal promoter recognition and transition from initiation to elongation.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Helen A. Beilinson, Rebecca A. Glynn, Anurupa Devi Yadavalli, Jianxiong Xiao, Elizabeth Corbett, Huseyin Saribasak, Rahul Arya, Charline Miot, Anamika Bhattacharyya, Jessica M. Jones, Jagan M. R. Pongubala, Craig H. Bassing, David G. Schatz
Summary: The RAG1 N-terminal region regulates V(D)J recombination and lymphocyte development through multiple pathways, including control of the balance between short- and long-range recombination, as shown in studies with different RAG1 mutant mice.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Chun-Chin Chen, Bo-Ruei Chen, Yinan Wang, Philip Curman, Helen A. Beilinson, Ryan M. Brecht, Catherine C. Liu, Ryan J. Farrell, Jaime de Juan-Sanz, Louis-Marie Charbonnier, Shingo Kajimura, Timothy A. Ryan, David G. Schatz, Talal A. Chatila, Jakob D. Wikstrom, Jessica K. Tyler, Barry P. Sleckman
Summary: SERCA proteins modulate intracellular Ca2+ levels to regulate RAG1 and RAG2 gene expression and V(D)J recombination, and defects in SERCA functions cause lymphopenia.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Chang Liu, Wei Shi, Scott T. Becker, David G. Schatz, Bin Liu, Yang Yang
Summary: This study highlights the crucial role of ExoN in the coronavirus life cycle, its recognition and excision of nucleotide analog inhibitors, and provides insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. The cryo-electron microscopy structures reveal the molecular determinants of ExoN substrate specificity, offering guidance for the rational design of improved anticoronavirus therapies.
Article
Immunology
Alina Tarsalainen, Yaakov Maman, Fei-Long Meng, Minna K. Kylaniemi, Anni Soikkeli, Paulina Budzynska, Jessica J. McDonald, Filip Senigl, Frederic W. Alt, David G. Schatz, Jukka Alinikula
Summary: Somatic hypermutation is driven by DIVACs, which increase phosphorylation and occupancy of RNA polymerase II, leading to accumulation of stalled Pol II and locus-specific targeting of SHM.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Environmental Sciences
Nicholas J. Nassikas, Elizabeth A. W. Chan, Christopher G. Nolte, Henry A. Roman, Niamh Micklewhite, Patrick L. Kinney, E. Jane Carter, Neal L. Fann
Summary: Exposure to PM2.5 is associated with asthma development and exacerbation in children. Future climate change may increase the concentration and distribution of PM2.5, leading to additional childhood asthma cases and albuterol inhaler use. These outcomes could be mitigated by reducing air pollution emissions.
AIR QUALITY ATMOSPHERE AND HEALTH
(2022)
Article
Cell Biology
Tingting Gan, Yuhong Wang, Yang Liu, David G. Schatz, Jiazhi Hu
Summary: RAG1 and RAG2 form a tetramer nuclease for V(D)J recombination in lymphocytes, with RAG1 requiring interaction with RAG2 to be activated. RAG2 disrupts RAG1 aggregates, activating recombination.
Article
Cell Biology
Lizhen Wu, Vipul Shukla, Anurupa Devi Yadavalli, Ravi K. Dinesh, Dijin Xu, Anjana Rao, David G. Schatz
Summary: The DNA repair factor HMCES can strongly suppress deletions, facilitating the production of antigen-specific antibodies. Their findings propose a novel model for protecting Ig gene integrity during SHM.
GENES & DEVELOPMENT
(2022)
Review
Immunology
Chang Liu, Yuhang Zhang, Catherine C. Liu, David G. Schatz
Summary: This review discusses the evolution of adaptive immunity in jawed vertebrates through antigen receptor gene assembly via V(D)J recombination, highlighting the functional and structural transitions that occurred during the evolution of RAG.
NATURE REVIEWS IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Marcel Kuhny, Lisa R. Forbes, Elif Cakan, Andrea Vega-Loza, Valentyna Kostiuk, Ravi K. Dinesh, Salome Glauzy, Asbjorg Stray-Pedersen, Ashley E. Pezzi, I. Celine Hanson, Alexander Vargas-Hernandez, Mina LuQuing Xu, Zeynep H. Coban-Akdemir, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Gibbs, James R. Lupski, Ivan K. Chinn, David G. Schatz, Jordan S. Orange, Eric Meffre
JOURNAL OF CLINICAL INVESTIGATION
(2020)