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
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
Cell Biology
Yolla German, Loan Vulliard, Anton Kamnev, Laurene Pfajfer, Jakob Huemer, Anna-Katharina Mautner, Aude Rubio, Artem Kalinichenko, Kaan Boztug, Audrey Ferrand, Joerg Menche, Loic Dupre
Summary: The immunological synapse decodes stimulatory signals into adapted lymphocyte responses, and high-content imaging is used to analyze T and NK cells. The study demonstrates how actin cytoskeleton remodeling shapes synapse architecture and affects lytic granule positioning. Analysis of immunodeficient individuals' CD8(+) T cells reveals the roles of ARPC1B and WASP in synapse assembly.
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.
Review
Cell Biology
Victor Calvo, Manuel Izquierdo
Summary: This paragraph discusses the formation of the immune synapse in T and B lymphocytes, which involves reorganization of F-actin and centrosome polarization. These processes occur during lytic granule degranulation in cytotoxic T lymphocytes and cytokine-containing vesicle secretion in T-helper lymphocytes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Loic Dupre, Kaan Boztug, Laurene Pfajfer
Summary: The actin cytoskeleton in T lymphocytes plays a crucial role in controlling key cellular activities like antigen scanning and sensing, and polarized delivery of effector molecules via the immunological synapse. This dynamic cytoskeleton remodeling is orchestrated by a complex program of multiple signaling pathways, involving the coordinated actions of various actin regulatory proteins.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Lyndsay Avery, Tanner F. Robertson, Christine F. Wu, Nathan H. Roy, Samuel D. Chauvin, Eric Perkey, Ashley Vanderbeck, Ivan Maillard, Janis K. Burkhardt
Summary: X-MAID is a primary immunodeficiency disease characterized by severe lymphopenia and recurrent infections. Using a mouse model, researchers found that the disease is caused by a mutation in the protein moesin. This model provides valuable insights into the complexity of immunodeficiency and the role of the actin cortex in lymphocyte function.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Hemant Joshi, Sharon Celeste Morley
Summary: This article summarizes how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances actin polymerization and promotes intercellular adhesion and immune synapse formation. LPL plays important roles in T-cell migration, activation, and cytokine production and proliferation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Nagaja Capitani, Cosima T. Baldari
Summary: Bacteria have evolved mechanisms to target host immune responses by affecting the assembly of the immunological synapse (IS), enabling evasion of immune defenses. Recent studies have shown that bacterial virulence factors directly impact IS assembly in T cells, potentially exploiting vulnerabilities related to IS in order to evade T cell-mediated immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chanchanok Chaichim, Tamara Tomanic, Holly Stefen, Esmeralda Paric, Lucy Gamaroff, Alexandra K. Suchowerska, Peter W. Gunning, Yazi D. Ke, Thomas Fath, John Power
Summary: The study found that, despite being enriched in dendritic spines, overexpression of Tpm3.1 does not significantly alter the morphology or function of dendritic spines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Eleonora Sarantelli, Apostolis Mourkakis, Lefteris C. Zacharia, Andreas Stylianou, Vasiliki Gkretsi
Summary: As metastasis is a major cause of cancer-related deaths, understanding the cellular and molecular events involved in cancer cell migration and invasion is crucial for developing novel anti-metastatic therapies. Fascin-1, an actin-bundling protein, plays a fundamental role in cell migration processes. It is significantly elevated in most cancers and its high expression is associated with aggressive disease and poor prognosis. Recent studies show that Fascin-1 is critically involved in metastasis and suggest it as a promising target for anti-metastatic treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Multidisciplinary Sciences
Sudha Kumari, Darrell Irvine
Summary: T lymphocytes detect pathogens through the interaction of their T cell receptor with pathogen-derived peptides presented on infected cells. The formation of immunological synapse between T cells and infected cells is crucial for T cell activation, involving dynamic actin polymerization.
JOURNAL OF THE INDIAN INSTITUTE OF SCIENCE
(2021)
Article
Multidisciplinary Sciences
Yashar Bashirzadeh, Hossein Moghimianavval, Allen P. Liu
Summary: Cell shape changes during locomotion and cytokinesis are primarily driven by myosin-induced remodeling of cortical actin patterns. The architecture of actin networks, which largely determines the shape of the membrane, is influenced by passive crosslinkers such as alpha-actinin and fascin, as well as the actin nucleator Arp2/3 complex. By reconstituting actomyosin networks in cell-sized lipid bilayer vesicles, the study shows that the size of the vesicle and the concentrations of alpha-actinin and fascin can lead to the assembly of different actomyosin patterns, such as rings and aster-like structures.
Article
Cell Biology
Laura Bozal-Basterra, Maria Gonzalez-Santamarta, Veronica Muratore, Natalia Martin-Martin, Amaia Ercilla, Jose A. Rodriguez, Arkaitz Carracedo, James D. Sutherland, Rosa Barrio
Summary: LUZP1 exhibits frequent genomic aberrations in cancer, particularly gene deletions, and its loss promotes cell migration, invasion, apoptosis, and alterations in cell morphology. Additionally, LUZP1 plays regulatory roles beyond actin filament bundling, affecting actin polymerization through changes in ACTR3 and phospho-cofilin ratios. These findings suggest a novel role for LUZP1 in cancer regulation through actin cytoskeleton control.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Celine Cuche, Marta Mastrogiovanni, Marie Juzans, Helene Laude, Marie-Noelle Ungeheuer, Daniel Krentzel, Maria Isabella Gariboldi, Daniel Scott-Algara, Marianne Madec, Sophie Goyard, Camille Floch, Gaelle Chauveau-Le Friec, Pierre Lafaye, Charlotte Renaudat, Muriel Le Bidan, Christine Micallef, Sandrine Schmutz, Sebastien Mella, Sophie Novault, Milena Hasan, Darragh Duffy, Vincenzo Di Bartolo, Andres Alcover
Summary: Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of colorectal adenomas with high risk of becoming colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene are often responsible for FAP. Our recent study suggests that the APC protein is involved in multiple phases of T cell responses. We investigated immune cell abnormalities in FAP subjects and found dysfunctions in various immune cell populations, gene expressions, cytokine and chemokine productions, and T cell migration.
FRONTIERS IN IMMUNOLOGY
(2023)
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)
Article
Chemistry, Multidisciplinary
Eike-Christian Wamho, Anna Romanov, Hellen Huang, Benjamin J. Read, Eric Ginsburg, Grant A. Knappe, Hyun Min Kim, Nicholas P. Farrell, Darrell J. Irvine, Mark Bathe
Summary: Viruslike particles (VLPs) fabricated using wireframe DNA origami are programmable platforms for vaccines and gene therapy. Researchers have found that inhibiting endonucleases with minor groove binders (MGBs) can increase the stability of these VLPs, making them more effective for therapeutic and vaccine applications.
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.
Article
Allergy
Erin Janssen, Mohammad F. Alosaimi, Anas M. Alazami, Abdullah Alsuliman, Ayodele Alaiya, Bandar Al-Saud, Hamoud Al-Mousa, Tariq Jassim Al-Zaid, Emma Smith, Craig D. Platt, Hibah Alruwaili, Sarah Albanyan, Sulaiman M. Al-Mayouf, Raif S. Geha
Summary: This study identified a homozygous mutation in FGL2 in a patient with impaired Treg cell function and immune dysregulation. The defect was rescued by the addition of soluble FGL2, suggesting its potential as a therapeutic option for this patient.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
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
Immunology
Amelie M. Jule, Ki Pui Lam, Maria Taylor, Kacie J. Hoyt, Kevin Wei, Maria Gutierrez-Arcelus, Siobhan M. Case, Mia Chandler, Margaret H. Chang, Ezra M. Cohen, Fatma Dedeoglu, Olha Halyabar, Jonathan Hausmann, Melissa M. Hazen, Erin Janssen, Jeffrey Lo, Mindy S. Lo, Esra Meidan, Jordan E. Roberts, Holly Wobma, Mary Beth F. Son, Robert P. Sundel, Pui Y. Lee, Peter T. Sage, Talal A. Chatila, Peter A. Nigrovic, Deepak A. Rao, Lauren A. Henderson
Summary: Tph cells play a crucial role in driving B cell maturation and antibody production in seropositive rheumatoid arthritis. In this study, the researchers investigated T cell-B cell interactions in juvenile oligoarthritis and found dysregulated Tph cells promoting B cell antibody production in the synovial fluid of patients with antinuclear antibodies. The single-cell transcriptomics analysis revealed the upregulation of B cell help-associated genes in Tph cells from ANA-positive patients. These findings highlight the central role of disordered T cell-help to B cells in autoantibody-positive arthritides.
FRONTIERS IN IMMUNOLOGY
(2023)
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.
Article
Chemistry, Multidisciplinary
Swati Kataria, Jifa Qi, Ching-Wei Lin, Zhongming Li, Eric L. Dane, Archana Mahadevan Iyer, Jay Sacane, Darrell J. Irvine, Angela M. Belcher
Summary: Only a minority of patients benefit from cancer immunotherapy, and researchers are actively trying to address this variability. The infiltration of immune cells into tumors is a vital indicator of response and survival, but noninvasive sampling of immune cells in the tumor microenvironment remains limited. In this study, researchers demonstrate the use of rare-earth nanocrystals for noninvasive imaging of tumor-infiltrating T-cells in an aggressive melanoma model.
Article
Rheumatology
Holly Wobma, Erin Janssen
Summary: Regulatory T cells (Tregs) are essential for immune tolerance, and disorders of Tregs can lead to immune dysregulation. This review focuses on monogenic inborn errors of immunity (IEIs) affecting Treg development, stability, and function, leading to autoimmune, atopic, and infectious manifestations.
RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
(2023)
Editorial Material
Rheumatology
Erin Janssen
RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
(2023)
Article
Multidisciplinary Sciences
Bingxu Liu, Rebecca J. Carlson, Ivan S. Pires, Matteo Gentili, Ellie Feng, Quentin Hellier, Marc A. Schwartz, Paul C. Blainey, Darrell J. Irvine, Nir Hacohen
Summary: The activation of STING leads to proton leakage from organelles, which triggers noncanonical lipidation of LC3B and inflammasome activation. Through structural analysis, it is suggested that STING functions as a proton channel. STING-induced proton flux in the Golgi and liposomes can be blocked by the STING agonist C53, leading to inhibition of LC3B lipidation and inflammasome activation. These findings demonstrate that the interferon-induction function of STING can be separated from its roles in LC3B lipidation and inflammasome activation.
Article
Chemistry, Multidisciplinary
Nicholas L. Truex, Aureïlie Rondon, Simon L. Ro''ssler, Cameron C. Hanna, Yehlin Cho, Bin-You Wang, Coralie M. Backlund, Emi A. Lutz, Darrell J. Irvine, Bradley L. Pentelute
Summary: This study engineered an antigen peptide delivery system to improve the efficacy of vaccines by targeting dendritic cells and facilitating cytosolic delivery. The results demonstrate that this system enhances immune responses and significantly inhibits tumor growth and improves survival rates in mice.
ACS CENTRAL SCIENCE
(2023)