Review
Immunology
Ray A. Ohara, Kenneth M. Murphy
Summary: Cross-priming, initially recognized in cytotoxic T lymphocyte (CTL) responses, involves the presentation of minor histocompatibility antigens by antigen presenting cells (APCs) derived from immunizing cells. As understanding of T cell receptor antigen recognition progressed, cross-priming was redefined as cross-presentation and expanded to include different forms of antigens and APCs not involved in in vivo CTL priming. In vitro cell models have been utilized for studying cross-presentation, but recent studies have shown differences between these models and in vivo APCs. Current research focuses on validating in vivo pathways and gene candidates for cross-presentation, and evaluating their contributions to CTL responses across different antigens and immunologic settings.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Oncology
Hongyan Ren, Yongbin Mou, Lin Lin, Lixin Wang, Hongming Hu
Summary: The research found that coating conventional aluminum adjuvants with polyethyleneimine (PEI) could enhance antigen cross-presentation of DCs, providing an alternative approach for the rapid translation of alumina nanoparticles adjuvants into clinical application. PEIs exerted differential effects on antigen cross-presentation, suggesting a potential for improving the efficacy of antigen delivery.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
(2021)
Article
Allergy
Janice J. Huang, Samantha B. Gaines, Mateo L. Amezcua, Tamar R. Lubell, Peter S. Dayan, Marissa Dale, Alexis D. Boneparth, Mark D. Hicar, Robert Winchester, Mark Gorelik
Summary: This study aimed to analyze the immunologic features of MIS-C patients compared to febrile controls. The results showed that elevated cytokines, activation of type 1 dendritic cells, and dysregulation of NK cells were key features in the pathophysiology of this syndrome.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Review
Medicine, Research & Experimental
Tingting Zhang, Adila Aipire, Yijie Li, Changying Guo, Jinyao Li
Summary: This review summarizes the mechanisms of cross-presentation (XPT) and its application in tumor immunotherapy. Dendritic cells enhance their antigen presentation capacity through receptor-mediated internalization of exogenous antigens, endosome escape, engagement of other XPT-related proteins, and the use of adjuvants, thereby improving the outcomes of DC-based therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Gaetan Barbet, Priyanka Nair-Gupta, Michael Schotsaert, Stephen T. Yeung, Julien Moretti, Fabian Seyffer, Giorgi Metreveli, Thomas Gardner, Angela Choi, Domenico Tortorella, Robert Tampe, Kamal M. Khanna, Adolfo Garcia-Sastre, J. Magarian Blander
Summary: The study explains how viruses target host cell antigen-processing pathways, focusing on MHC-I molecules and the re-routing of ERGIC-resident MHC molecules to phagosomal vesicles for cross-presentation. It suggests that even without TAP, protective CD8(+) T cells can still be mobilized during viral infection, highlighting a noncanonical cross-presentation pathway.
Review
Immunology
Christophe Macri, Devi Jenika, Cassandra Ouslinis, Justine D. Mintern
Summary: Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in adaptive immunity. Targeting antigen directly to DCs is a selective vaccination strategy that takes advantage of the antigen uptake and presentation functions of DC subsets. This review focuses on DC-targeted vaccination strategies aimed at inducing effective cross-presentation for CD8+ T cell immunity. Receptors highly expressed by mouse and human cDCs, such as DEC205, Clec9A, and XCR1, are explored. The outcomes of DC-targeted vaccination in mouse models and human clinical trials are discussed, highlighting its potential for the prevention and treatment of tumors and infectious diseases.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Oncology
Camille Le Gall, Anna Cammarata, Lukas de Haas, Ivan Ramos-Tomillero, Jorge Cuenca-Escalona, Kayleigh Schouren, Zacharias Wijfjes, Anouk M. D. Becker, Johanna Bodder, Yusuf Dolen, I. Jolanda M. de Vries, Carl G. Figdor, Georgina Florez-Grau, Martijn Verdoes
Summary: Background Type 1 conventional dendritic cells (cDC1s) have the potential to induce potent CD8(+) T cell responses, making them an ideal target for delivering antigens in novel vaccination strategies. XCR1, a seven transmembrane G protein-coupled receptor uniquely expressed by cDC1s, has been identified as an attractive receptor for antigen delivery. In this study, researchers explored the delivery of tumor antigens to human cDC1s by conjugating XCL1 (a ligand that binds to XCR1) with an analog of the HLA-A*02:01 epitope of the cancer testis antigen NY-ESO-1. The results showed that PEGylated XCL1-antigen conjugates retained binding to XCR1 and induced cDC1 chemoattraction. The model epitope was efficiently cross-presented by human cDC1s, leading to the activation of NY-ESO-1-specific CD8(+) T cells. Targeting XCR1 at the surface of cDC1s increased the vaccine activity. This study presents a novel strategy for generating targeted vaccines fused to insoluble antigens and highlights the potential of targeting XCR1 to induce potent CD8(+) T cell responses in human cDC1s.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Diego Del Balzo, Anahi Capmany, Ignacio Cebrian, Maria Teresa Damiani
Summary: This study reveals that Chlamydia trachomatis can induce productive infections in murine dendritic cells and disrupt MHC-I trafficking, leading to impaired antigen cross-presentation ability.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Cristina Croce, Facundo Garrido, Sofia Dinamarca, Julien Santi-Rocca, Sabrina Marion, Nicolas Blanchard, Luis S. Mayorga, Ignacio Cebrian
Summary: Dendritic cells are crucial for antigen presentation and Toxoplasma gondii infection. Cholesterol trafficking and multivesicular body formation play important roles in the optimal functioning of dendritic cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Patrick Fernandes Rodrigues, Athanasios Kouklas, Grozdan Cvijetic, Nicolas Bouladoux, Mladen Mitrovic, Jigar V. Desai, Djalma S. Lima-Junior, Michail S. Lionakis, Yasmine Belkaid, Robert Ivanek, Roxane Tussiwand
Summary: Plasmacytoid dendritic cells (pDCs) play a critical role in immune responses, but recent studies have discovered a previously unknown immune subset called pDC-like cells. These cells not only resemble pDCs but also have features of conventional DCs (cDCs). It has been found that a significant proportion of cDC2s originate from these pDC-like cells, which can be referred to as pre-DC2. This precursor subset responds to homeostatic cytokines and differentiates into cDC2, which prime T helper 17 (TH17) cells. The development of pre-DC2 into specific cDC2 subsets requires the transcription factor KLF4 and plays a role in regulating immune responses at barrier sites.
SCIENCE IMMUNOLOGY
(2023)
Article
Pediatrics
Sebastian Wirsching, Marina Machtakova, Frauke Borgans, Leah Pretsch, Michael Fichter, Maximiliano L. Cacicedo, Heloise Therien-Aubin, Katharina Landfester, Stephan Gehring
Summary: Childhood mortality is a significant issue, with a large number of deaths attributed to preventable infectious diseases. The study demonstrates the superior ability of the TLR7/8 agonist R848 in activating the immune system of both adults and neonates. Furthermore, R848 can be efficiently delivered along with antigens using nanocapsules, offering new possibilities for vaccine development.
FRONTIERS IN PEDIATRICS
(2022)
Review
Immunology
Izumi Sasaki, Takashi Kato, Hiroaki Hemmi, Yuri Fukuda-Ohta, Naoko Wakaki-Nishiyama, Asumi Yamamoto, Tsuneyasu Kaisho
Summary: Dendritic cells (DC) are essential in connecting innate and adaptive immunity. Among the subsets, cDC1 plays a critical role in maintaining intestinal immune homeostasis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Ichwaku Rastogi, Douglas G. McNeel
Summary: DNA vaccines have shown limited immunogenicity in human clinical trials. B cells, not DCs, are the primary antigen-presenting cells for DNA-encoded antigens. B cells can translate the encoded antigens, but DCs are required for activating CD8 T cells. Further study of B cells as APCs is important for improving the efficacy of DNA vaccines.
Article
Biochemistry & Molecular Biology
Lisa G. M. Huis In 't Veld, Nataschja Ho, Melisssa Wassink, Martijn H. den Brok, Gosse J. Adema
Summary: Saponin-based adjuvants (SBAs) are a promising new type of adjuvant that can enhance dendritic cell-mediated antigen cross-presentation and activate CD8 + T cells by inducing lipid bodies. The study reveals that SBAs specifically induce the PERK pathway and depend on its activation for dendritic cell cross-presentation. Additionally, the MHCII(lo)CD11b(hi) subset of dendritic cells shows the highest responsiveness to SBAs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Immunology
Nataschja I. Ho, Marcel G. Camps, Juan J. Garcia-Vallejo, Erik Bos, Abraham J. Koster, Martijn Verdoes, Yvette van Kooyk, Ferry Ossendorp
Summary: Dendritic cells have the unique ability to present exogenous antigens through MHC class I molecules, with the antigen being conserved in storage compartments for days. These compartments in DCs lack certain molecules involved in MHC class I processing, and the co-localization of active cathepsin X with protein antigen suggests a novel role for cathepsin X in antigen processing and cross-presentation. These compartments can preserve protein antigens from different uptake routes and contribute to long-lasting antigen cross-presentation.
Article
Allergy
Miriam Gross, Carsten Speckmann, Annette May, Tania Gajardo-Carrasco, Katharina Wustrau, Sarah Lena Maier, Marcus Panning, Daniela Huzly, Abbas Agaimy, Yenan T. Bryceson, Sharon Choo, C. W. Chow, Gregor Dueckers, Anders Fasth, Sylvie Fraitag, Katja Graewe, Sabine Haxelmans, Dirk Holzinger, Ole Hudowenz, Judith M. Huebschen, Claudia Khurana, Korbinian Kienle, Roman Klifa, Klaus Korn, Heinz Kutzner, Tim Laemmermann, Svea Ledig, Dan Lipsker, Marie Meeths, Nora Naumann-Bartsch, Jelena Rascon, Anne Schaenzer, Maximilian Seidl, Bianca Tesi, Christelle Vauloup-Fellous, Beate Vollmer-Kary, Klaus Warnatz, Claudia Wehr, Benedicte Neven, Pablo Vargas, Fernando E. Sepulveda, Kai Lehmberg, Annette Schmitt-Graeff, Stephan Ehl
Summary: This study investigated the defective effector mechanism allowing rubella vaccine virus persistence in granulomas by studying patients with cytotoxicity defects and granuloma. The results suggest a critical role of T cells in rubella elimination.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Sebastian Montealegre, Elise Lebigot, Hugo Debruge, Norma Romero, Benedicte Heron, Pauline Gaignard, Antoine Legendre, Apolline Imbard, Stephanie Gobin, Emmanuelle Lacene, Patrick Nusbaum, Arnaud Hubas, Isabelle Desguerre, Aude Servais, Pascal Laforet, Peter van Endert, Francois Jerome Authier, Cyril Gitiaux, Pascale de Lonlay
Summary: This study characterizes the clinical and biological traits of two individuals with variants in ISCU and FDX2, finding that the individual with FDX2 variants is more severely affected.
NEUROLOGY-GENETICS
(2022)
Article
Chemistry, Multidisciplinary
Leishemba K. Thoidingjam, Cedric M. Blouin, Christine Gaillet, Aurelien Brion, Stephanie Solier, Supaporn Niyomchon, Ahmed El Marjou, Sara Mouasni, Fernando E. Sepulveda, Genevieve de Saint Basile, Christophe Lamaze, Raphael Rodriguez
Summary: Interferons (IFNs), important cytokines, play roles in triggering downstream biochemical events upon binding to cell surface receptors. Dysregulated IFN signaling has been linked to cancer progression and autoimmune diseases. Researchers have identified a small molecule that can block the activation of IFN signaling and further developing a more potent analogue that shows potential therapeutic effects in reducing bleeding in a model of hemorrhagic colitis. This first-in-class small molecule also inhibits other types of IFN-induced signaling. This research provides a foundation for the development of pan-IFN inhibitory drugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Allergy
Cyril Longe, Manuela Bratti, Mathieu Kurowska, Shamila Vibhushan, Pierre David, Valere Desmeure, Jian-Dong Huang, Alain Fischer, Genevieve de Saint Basile, Fernando E. Sepulveda, Ulrich Blank, Gael Menasche
Summary: This study demonstrates the crucial role of Rab44 in regulating secretory granule transport during degranulation in mast cells. Deficiency in Rab44 impairs granule translocation and degranulation, leading to reduced sensitivity to IgE-mediated allergic reactions. Rab44 can be considered a potential target for modulating MC degranulation and inhibiting allergic reactions.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Cell Biology
Phillip Pymm, Stefan Tenzer, Edmund Wee, Mirjana Weimershaus, Anne Burgevin, Simon Kollnberger, Jan Gerstoft, Tracy M. Josephs, Kristin Ladell, James E. McLaren, Victor Appay, David A. Price, Lars Fugger, John I. Bell, Hansjoerg Schild, Peter van Endert, Maria Harkiolaki, Astrid K. N. Iversen
Summary: This study discovers that the cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a specific epitope in the human immunodeficiency virus are associated with enhanced immune control. The length and mutations of the epitope influence the CTL and NK cell responses, leading to viral escape.
Article
Oncology
Lucillia Bezu, Alejandra Wu Chuang, Allan Sauvat, Juliette Humeau, Wei Xie, Giulia Cerrato, Peng Liu, Liwei Zhao, Shuai Zhang, Julie Le Naour, Jonathan Pol, Peter van Endert, Oliver Kepp, Fabrice Barlesi, Guido Kroemer
Summary: This study investigates the anticancer effects of six local anesthetics used in clinical practice. The results suggest that local anesthetics induce immunogenic stress responses in cancer cells, leading to antitumor effects.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biophysics
Ambroise Marcais, Nizar Mahlaoui, Benedicte Neven, Fanny Lanternier, Emilie Catherinot, Helene Salvator, Morgane Cheminant, Maxime Jeljeli, Vahid Asnafi, Peter van Endert, Louis-Jean Couderc, Olivier Lortholary, Capucine Picard, Despina Moshous, Olivier Hermine, Alain Fischer, Felipe Suarez
Summary: Allo-HSCT is an effective and safe treatment for young adults with primary immunodeficiency disease (PID), with acceptable toxicity and clinical improvement.
BONE MARROW TRANSPLANTATION
(2022)
Article
Pharmacology & Pharmacy
Liting Wang, Fabien Hubert, Sarah Idres, Milia Belacel-Ouari, Valerie Domergue, Severine Domenichini, Florence Lefebvre, Delphine Mika, Rodolphe Fischmeister, Veronique Leblais, Boris Manoury
Summary: Phosphodiesterases (PDE) type 3 and 4 promote vasoconstriction by hydrolysing cAMP. In experimental heart failure (HF), PDE3 makes PDE4 redundant in aorta, but it is not known if this occurs in resistance vessels, such as mesenteric artery. As PDE2 is increased in the failing myocardium, its possible role in the vasculature also needs to be addressed.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Editorial Material
Immunology
Jonas Kuiper, Peter van Endert
Summary: The Black Death, caused by Yersinia pestis infection, was a devastating pandemic in the 14th century that posed a significant challenge to human immune defenses. A recent study suggests that a genetic variant in an antigen-processing gene may have provided survival advantage during the plague and underwent rapid genomic selection in Europeans.
TRENDS IN IMMUNOLOGY
(2023)
Article
Hematology
Charlotte Boussard, Laure Delage, Tania Gajardo, Alexandre Kauskot, Maxime Batignes, Nicolas Goudin, Marie -Claude Stolzenberg, Camille Brunaud, Patricia Panikulam, Quentin Riller, Maryse Moya-Nilges, Jean Solarz, Christelle Reperant, Beatrice Durel, Jean-Claude Bordet, Olivier Pelle, Corinne Lebreton, Aude Magerus, Vithura Pirabakaran, Pablo Vargas, Sebastien Dupichaud, Marie Jeanpierre, Angelique Vinit, Mohammed Zarhrate, Cecile Masson, Nathalie Aladjidi, Peter D. Arkwright, Brigitte Bader-Meunier, Sandrine Baron Joly, Joy Benadiba, Elise Bernard, Dominique Berrebi, Christine Bodemer, Martin Castelle, Fabienne Charbit-Henrion, Marwa Chbihi, Agathe Debray, Philippe Drabent, Sylvie Fraitag, Miguel Hie, Judith Landman-Parker, Ludovic Lhermitte, Despina Moshous, Pierre Rohrlich, Frank Ruemmele, Anne Welfringer-Morin, Maud Tusseau, Alexandre Belot, Nadine Cerf-Bensussan, Marie Roelens, Capucine Picard, Benedicte Neven, Alain Fischer, Isabelle Callebaut, Mickael Menager, Fernando E. Sepulveda, Frederic Adam, Frederic Rieux-Laucat
Summary: DOCK11 deficiency leads to impaired cellular function and immune dysregulation, resulting in autoimmune disorders.
Article
Biochemistry & Molecular Biology
Ayse Yilmaz, Chiara Guerrera, Emmanuelle Waeckel-Enee, Joanna Lipecka, Barbara Bertocci, Peter van Endert
Summary: Insulin-degrading enzyme (IDE) is mainly localized in the cytosol and has additional functions beyond insulin degradation. It interacts with multiple mitochondrial ribosomal proteins and proteins involved in mitochondrial complex synthesis and assembly. The mitochondrial interactomes of wild type and mutant IDE are similar and do not reveal proteolytic IDE substrates. IDE may have non-proteolytic functions in mitochondria, acting as a chaperone and contributing to protein homeostasis and stress responses.
Review
Immunology
Irini Evnouchidou, Despoina Koumantou, Mathilde Nugue, Loredana Saveanu
Summary: Antigen-trimming aminopeptidases, belonging to the oxytocinase subfamily of M1 metallopeptidases, have been extensively studied for their ability to modify antigenic precursors and generate major histocompatibility class-I ligands. These enzymes have been associated with autoimmune diseases, cancers, and infections, and recent research has raised new questions about their functions.
CURRENT OPINION IN IMMUNOLOGY
(2023)
Article
Allergy
Tania Gajardo, Mathilde Bernard, Marie Lo, Elisa Turck, Claire Leveau, Marie-Therese EI-Daher, Alexandre Deslys, Patricia Panikulam, Constantin Menche, Mathieu Kurowska, Gregoire Le Lay, Lucie Barbier, Despina Moshous, Benedicte Neven, Henner F. Farin, Alain Fischer, Gael Menasche, Genevieve de Saint Basile, Pablo Vargas, Fernando E. Sepulveda
Summary: This study investigates the impact of TTC7A deficiency on immune homeostasis and reveals that TTC7A-deficient lymphocytes exhibit altered cell migration and impaired actin dynamics. These findings suggest that TTC7A plays a critical role in lymphocyte migration and is likely to contribute to the progressive immunodeficiency in patients.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Samira Benadda, Mathilde Nugue, Despoina Koumantou, Marcelle Bens, Mariacristina De Luca, Olivier Pelle, Renato C. Monteiro, Irini Evnouchidou, Loredana Saveanu
Summary: This study investigated the involvement of endosomal signaling in the function of human receptors for Fc immunoglobulin fragments (FcRs). The results showed that Fc alpha RI was targeted directly to lysosomes, while Fc gamma RIIA and Fc gamma RI were internalized in specific endosomal compartments described by IRAP. The destabilization of Fc gamma R endosomal signaling compromised cytokine secretion and macrophage ability to kill tumor cells by ADCC.
Review
Biochemistry & Molecular Biology
Irini Evnouchidou, Vivien Caillens, Despoina Koumantou, Loredana Saveanu
Summary: This study reviews the molecular mechanisms of TCR endocytosis and recycling and discusses the impact of endosomal TCR signaling on T cell activation.
BIOMEDICAL JOURNAL
(2022)
