Article
Multidisciplinary Sciences
En Cai, Casey Beppler, John Eichorst, Kyle Marchuk, Scott W. Eastman, Matthew F. Krummel
Summary: This study demonstrates the randomness of receptor patch localization within the membrane and on microvillar projections prior to antigen detection, which may play a role in the generation of multiple individually composed receptor patch compositions at a single synapse.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Bonah Kim, Hee Young Kim, Won-Woo Lee
Summary: Zinc, an essential microelement, plays immunoregulatory roles by influencing signaling pathways to enhance immune function. Zinc deficiency impairs immunity and increases susceptibility to infection. The interaction between Zip6-mediated zinc influx and TCR activation regulates T-cell responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Jose Luis Rodriguez-Fernandez, Olga Criado-Garcia
Summary: Dendritic cells are powerful antigen-presenting cells that control T cell activation through the immunological synapse. While most studies focus on the T cell side, dendritic cell side also plays a significant role in T cell activation, especially through actin polarization at the IS.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Huiping Shi, Bojing Shao
Summary: This review briefly summarizes the activation and roles of LFA-1 with varied ligand-binding affinities in the regulation of T-cell migration and immunological synapse formation.
Article
Cell Biology
Juan Jose Saez, Stephanie Dogniaux, Massiullah Shafaq-Zadah, Ludger Johannes, Claire Hivroz, Andres Ernesto Zucchetti
Summary: The paragraph discusses the important role of LAT in the signaling cascade induced by TCR activation, and its distribution and trafficking pathways in T cells upon activation. It shows that different proteins play specific roles in regulating the retrograde and anterograde transport of LAT during T cell activation.
Article
Biochemistry & Molecular Biology
Rui Fan, Hongwei Jiang, Yuntao Hu, Yueyue Xu, Yifei Zhou, Ganyi Chen, Yafeng Liu, Yiwei Yao, Wei Qin, Wen Chen, Fuhua Huang, Xin Chen
Summary: Myocytes experiencing hypoxia can attract macrophages and initiate inflammation around the injury area. Mitochondrial dysfunction is associated with macrophage pyroptosis. Stomatin-like protein-2 (SLP-2) is capable of regulating mitochondrial biogenesis and function. Whether SLP-2 affects macrophage pyroptosis was investigated in this study. The results showed that the deficiency of SLP-2 in macrophages enhanced the expression of NLRP3, GSDMD-N, and caspase-11, indicating an increased macrophage pyroptosis. SLP-2 deficiency also led to higher levels of ROS release and programmed death in macrophages. Additionally, the deletion of SLP-2 resulted in decreased mitochondrial function and increased mitochondrial damage. The expression level of HIF-1a was increased in SLP-2 deletion macrophages under LPS and Nigericin stimulation. The study suggests that SLP-2 can reduce macrophage pyroptosis and ameliorate hypoxia-induced injury in H9c2 cells by protecting mitochondrial function.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Wei Lin, Shuping Zhou, Meng Feng, Yong Yu, Qinghong Su, Xiaofan Li
Summary: The study demonstrated that sCD83 inhibits T cell activation by disrupting DC-T contact and immunological synapse formation, mainly through disrupting F-actin rearrangements in dendritic cells. This novel signaling pathway may be a potential target for developing new immunosuppressive therapies for autoimmune diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Juncal Fernandez-Orth, Leoni Rolfes, Lukas Gola, Stefan Bittner, Joseph Andronic, Vladimir L. Sukhorukov, Dmitri Sisario, Peter Landgraf, Daniela C. Dieterich, Manuela Cerina, Karl-Heinz Smalla, Thilo Kaehne, Thomas Budde, Stjepana Kovac, Tobias Ruck, Markus Sauer, Sven G. Meuth
Summary: The immunological synapse is a junction between a T cell and an antigen-presenting cell, involving CRAC, K(v)1.3, and KCa3.1 channels. TASK2 channels are newly identified players recruited to the immunological synapse, potentially contributing to T cell activation and treatment of autoimmune diseases.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mauro Serricchio, Peter Butikofer
Summary: The deletion of the Trypanosoma brucei homolog TbSlp2 gene has no effect on respiratory protein complex stability and mitochondrial functions under normal culture conditions, and is dispensable for the growth of T. brucei parasites. Additionally, TbSlp2 binds to the metalloprotease TbYme1 to form a large mitochondrial protein complex, where they negatively regulate each other's expression levels by accelerating protein turnover. The TbYme1 protein plays a role in heat-stress resistance, causing mitochondrial fragmentation and loss of viability in TbYme1 knock-out parasites cultured at elevated temperatures.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Medicine, Research & Experimental
Tusar Kanta Acharya, Shamit Kumar, Tejas Pravin Rokade, Young-Tae Chang, Chandan Goswami
Summary: The activation of T cells is influenced by temperature and intracellular calcium signaling. TRPV4, a non-selective calcium channel, is expressed in T cells and located in their mitochondria. Activation of TRPV4 increases mitochondrial calcium levels and affects mitochondrial temperature and metabolism.
Article
Chemistry, Multidisciplinary
Lukas Velas, Mario Brameshuber, Johannes B. Huppa, Elke Kurz, Michael L. Dustin, Philipp Zelger, Alexander Jesacher, Gerhard J. Schuetz
Summary: This study utilized 3D-SMLM technique to accurately measure the three-dimensional topography of the immunological synapse, revealing the interface characteristics and cleft size between T-cells and antigen-presenting cells.
Review
Cardiac & Cardiovascular Systems
Yuntao Hu, Yueyue Xu, Wen Chen, Zhibing Qiu
Summary: Stomatin-like protein-2 (SLP-2) is a mitochondrial-associated protein abundant in cardiomyocytes, which plays a crucial role in protecting mitochondria and has the potential to be a new target for the treatment of mitochondrial cardiomyopathy. Current studies have shown that SLP-2 maintains mitochondrial stability and function through various pathways.
HEART LUNG AND CIRCULATION
(2021)
Review
Biochemistry & Molecular Biology
Yuan-Tung Chu, Min-Tser Liao, Kuo-Wang Tsai, Kuo-Cheng Lu, Wan-Chung Hu
Summary: A comprehensive framework has been established to understand immunological pathways, and specific associations between immune responses and immune receptors have been identified. These findings contribute to the identification of biomarkers for immune cells and provide insights into host immunological pathways.
Review
Immunology
Elena Ockfen, Liza Filali, Diogo Pereira Fernandes, Celine Hoffmann, Clement Thomas
Summary: This review article emphasizes the importance of actin dynamics within the immunological synapse between cytotoxic lymphocytes and cancer cells, presenting emerging evidence that actin dynamics in cancer cells can critically influence the outcome of cytotoxic lymphocyte interactions with cancer cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stacie Shiqi Wang, Kylie Luong, Fiona Margaret Gracey, Shereen Jabar, Brad McColl, Ryan Stanley Cross, Misty Rayna Jenkins
Summary: CAR T cell therapy re-engineers patient-derived T cells to express a specific receptor targeting tumor antigens. Studies have shown that pMHCI-specific CARs can effectively recognize and kill tumor cells, forming a TCR-like immune synapse that enhances killing kinetics.
Editorial Material
Immunology
Hannah Dada, Michael L. Dustin
Summary: This study tells the different states of three tumor infiltrating lymphocytes, including exhaustion, inertness, and optimal status.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Jesse Goyette, David Depoil, Zhengmin Yang, Samuel A. Isaacson, Jun Allard, P. Anton van der Merwe, Katharina Gaus, Michael L. Dustin, Omer Dushek
Summary: Protein-protein binding domains, such as the Src homology 2 (SH2) domains, play a critical role in signaling networks. Tandem SH2 domains can enhance binding affinity and specificity, but there is a trade-off between long-lived binding and rapid signaling reversal. This study shows that phosphatases can accelerate the unbinding rate of tandem SH2 domains, breaking the trade-off and allowing for efficient T cell antigen discrimination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Mohammad Ameen Al-Aghbar, Ashwin K. Jainarayanan, Michael L. Dustin, Steve R. Roffler
Summary: This study proposes a TCR Bending Mechanosignal (TBM) model which suggests that local mechanical membrane bending of T cells on the nanometer scale may influence T cell receptor binding events and thus T-cell activation. The model highlights how the bending of the T cell membrane can enhance signaling and facilitate better recognition of antigens.
COMMUNICATIONS BIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Agnel Sfeir, Gord Fishell, Alexander F. Schier, Michael L. Dustin, Wen-Biao Gan, Alexandra Joyner, Ruth Lehmann, David Ron, David Roth, William S. Talbot, Deborah Yelon, Arturo Zychlinsky
Summary: Support for basic science has been overshadowed by initiatives focusing on specific medical issues, such as the recent dismantling of the Skirball Institute at NYU School of Medicine. This article reflects on the accomplishments and mission of Skirball, highlighting the benefits of maintaining a vision for basic science within academia.
Editorial Material
Immunology
Santosha Vardhana, Michael L. L. Dustin
Summary: This article discusses the role of spinach in enhancing strength and defending against bullies, and the importance of dietary magnesium ion deficiency affecting the activity of the key molecule LFA-1, which hinders the ability of CD8(+) T cells to combat various bullies.
TRENDS IN IMMUNOLOGY
(2022)
Review
Neurosciences
Olive Jung, Alec Thomas, Scott R. Burks, Michael L. Dustin, Joseph A. Frank, Marc Ferrer, Eleanor Stride
Summary: This review examines the evidence for inflammation associated with ultrasound-induced disrupted blood-brain barrier and discusses potential strategies to manage these inflammatory effects for improved therapeutic ultrasound efficacy and safety in neurological applications.
TRENDS IN NEUROSCIENCES
(2022)
Article
Multidisciplinary Sciences
Hsin-Fang Chang, Claudia Schirra, Momchil Ninov, Ulrike Hahn, Keerthana Ravichandran, Elmar Krause, Ute Becherer, Stefan Balint, Maria Harkiolaki, Henning Urlaub, Salvatore Valitutti, Cosima T. Baldari, Michael L. Dustin, Reinhard Jahn, Jens Rettig
Summary: In this study, we used a new method to isolate and observe the fusion of cytotoxic granules in CTLs. We found two classes of fusion-competent granules that release different types of cytotoxic proteins during fusion. These findings reveal the mechanism by which CTLs kill target cells.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Zhixin Jing, Mark J. McCarron, Michael L. Dustin, David R. Fooksman
Summary: This study reveals that the density of cognate peptide-MHCII (pMHCII) plays a quantitative role in instructing selection and cell fate decisions. By using differential delivery of OVA peptides to GC B cells based on DEC205 allelic copy number, the study shows that an increase in antigen uptake leads to proportional TFH cell help and B cell expansion. The results are further validated by the establishment of a caged OVA peptide. Differential CD40 signaling is found to be both necessary and sufficient for mediating differences in B cell expansion. The study also distinguishes the roles of TFH cells in expansion versus differentiation.
Article
Multidisciplinary Sciences
Pablo F. Cespedes, Michael L. Dustin
Summary: This paper presents a protocol for using Bead-Supported Lipid Bilayers (BSLBs) as antigen-presenting cell (APC) mimetics to capture and analyze trans-synaptic particles. The protocol also includes absolute measurements of protein densities on cell surfaces, reconstitution of BSLBs with physiological levels, and a flow cytometry procedure for tracking synaptic particle release by T cells. The protocol can be adapted to study the effects of various factors on T cell effector output.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Multidisciplinary Sciences
Pablo F. Cespedes, Ashwin Jainarayanan, Lola Fernandez-Messina, Salvatore Valvo, David G. Saliba, Elke Kurz, Audun Kvalvaag, Lina Chen, Charity Ganskow, Huw Colin-York, Marco Fritzsche, Yanchun Peng, Tao Dong, Errin Johnson, Jesus A. Siller-Farfan, Omer Dushek, Erdinc Sezgin, Ben Peacock, Alice Law, Dimitri Aubert, Simon Engledow, Moustafa Attar, Svenja Hester, Roman Fischer, Francisco Sanchez-Madrid, Michael L. Dustin
Summary: The authors use bead-supported lipid bilayers as synthetic APCs to show that trans-synaptic vesicles produced by T cells in the immunological synapse carry specialized cargos distinct from constitutive extracellular vesicles to serve as intercellular messengers.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Alessio Lanna, Bruno Vaz, Clara D'Ambra, Salvatore Valvo, Claudia Vuotto, Valerio Chiurchiu, Oliver Devine, Massimo Sanchez, Giovanna Borsellino, Arne N. Akbar, Marco De Bardi, Derek W. Gilroy, Michael L. Dustin, Brendan Blumer, Michael Karin
Summary: It was discovered that some T cells can elongate telomeres by acquiring telomere vesicles from antigen-presenting cells, independently of telomerase action, which contributes to delaying the aging process.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Audun Kvalvaag, Salvatore Valvo, Pablo F. Cespedes, David G. Saliba, Elke Kurz, Kseniya Korobchevskaya, Michael L. Dustin
Summary: Ligation of TCR to pMHC induces TCR ubiquitination and either internalization by T cell or release in extracellular vesicles. Clathrin-mediated ectocytosis facilitates the release of TCR, while clathrin-mediated trans-endocytosis enables the uptake of pMHC-TCR conjugates from the APC.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Alexander M. Morch, Falk Schneider, Edward Jenkins, Ana Mafalda Santos, Scott E. Fraser, Simon J. Davis, Michael L. Dustin
Summary: The sensitivity of the α(3) T cell receptor (TCR) is enhanced by the coreceptors CD4 and CD8 α(3). We found that the interaction between CD4 and Lck is stoichiometric and the interaction between CD8 α(3) and Lck is substantial. These findings help settle the question of kinase occupancy and suggest that the binding advantages that CD4 has over CD8 could be important when Lck levels are limiting.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Yavuz F. Yazicioglu, Eros Marin, Ciaran Sandhu, Silvia Galiani, Iwan G. A. Raza, Mohammad Ali, Barbara Kronsteiner, Ewoud B. Compeer, Moustafa Attar, Susanna J. Dunachie, Michael L. Dustin, Alexander J. Clarke
Summary: Clarke and colleagues discovered that germinal center B cells have dynamic mitochondria regulated by the transcription factor TFAM. TFAM helps the B cells enter the germinal center reaction by modulating cellular motility. Understanding this mechanism is important as germinal center B cells undergo rapid proliferation in a hypoxic microenvironment.
Article
Multidisciplinary Sciences
Ashwin Jainarayanan, Nithishwer Mouroug-Anand, Edward H. Arbe-Barnes, Adam J. Bush, Rachael Bashford-Rogers, Adam Frampton, Lara Heij, Mark Middleton, Michael L. Dustin, Enas Abu-Shah, Shivan Sivakumar
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a low 5-year survival rate of less than 8% due to its complex biology. Understanding the functional dynamics of T cells in the PDAC microenvironment is crucial for developing alternative therapeutic strategies, as PDAC is resistant to immunotherapy.