Article
Immunology
Peter W. West, Rajia Bahri, Karen M. Garcia-Rodriguez, Georgia Sweetland, Georgia Wileman, Rajesh Shah, Angeles Montero, Laura Rapley, Silvia Bulfone-Paus
Summary: Aberrant mast cell responses and complement activation both contribute to allergic diseases. IL-33 plays a critical role in regulating mast cell responses to complement anaphylatoxins, enhancing mast cell reactivity to C3a and C5a. This cross-regulation may aggravate Th2 immune responses and targeting anti-IL33 therapeutically could provide a rationale in allergic diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Kanan Bando, Yukinori Tanaka, Saka Winias, Shunji Sugawara, Itaru Mizoguchi, Yasuo Endo
Summary: IL-33 is released upon cell injury and induces histamine release and local inflammation. IL-33 directly and indirectly induces histamine release through histidine decarboxylase (HDC), and the newly formed histamine contributes to the negative regulation of IL-33-induced eosinophilia via H4 receptors.
INFLAMMATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Tiago C. Luis, Nikolaos Barkas, Joana Carrelha, Alice Giustacchini, Stefania Mazzi, Ruggiero Norfo, Bishan Wu, Affaf Aliouat, Jose A. Guerrero, Alba Rodriguez-Meira, Tiphaine Bouriez-Jones, Iain C. Macaulay, Maria Jasztal, Guangheng Zhu, Heyu Ni, Matthew J. Robson, Randy D. Blakely, Adam J. Mead, Claus Nerlov, Cedric Ghevaert, Sten Eirik W. Jacobsen
Summary: In this study, the researchers uncover a feedback mechanism in which IL-1 secreted by activated platelets signals through niche Lepr+ cells to activate HSCs and restore platelet homeostasis.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Isabel Peters, Sylvia Mueller, Claudia Kuechler, Ute Jaeger, Sebastian Drube
Summary: IL-33 induces the activation of signaling pathways in MCs, leading to the production of pro-inflammatory cytokines and allergic reactions. HSP90, which is upregulated during allergic reactions, plays a role in stabilizing cytokine mRNA and facilitating cytokine production. Therefore, targeting HSP90 could be a potential therapeutic intervention for blocking IL-33-mediated inflammatory reactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Pio Conti, Fabrizio E. Pregliasco, Rosa G. Bellomo, Carla E. Gallenga, Alessandro Caraffa, Spyros K. Kritas, Dorina Lauritano, Gianpaolo Ronconi
Summary: Psoriasis is a skin disease characterized by autoimmune features and inflammatory symptoms, often accompanied by various comorbidities. Immune cells like MCs and cytokines such as IL-36 play significant roles in the inflammation process of psoriasis, while IL-38 and IL-37 may serve as potential therapeutic tools for inhibiting inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Irene Tsilioni, Theoharis C. C. Theoharides
Summary: SARS-CoV-2 infects cells by binding its spike protein to ACE2 receptors, resulting in the production of proinflammatory cytokines and causing COVID-19. This study used human cultured mast cells to demonstrate that the SARS-CoV-2 full-length S protein, but not its receptor-binding domain, stimulates the secretion of proinflammatory cytokines and proteolytic enzymes. The secretion is further enhanced by interleukin-33 (IL-33), and the effect is mediated by toll-like receptor 4 (TLR4) for cytokines and ACE2 for enzymes. These findings suggest potential targeted treatments for inflammation caused by SARS-CoV-2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Charlene Akoto, Anna Willis, Chiara F. Banas, Joseph A. Bell, Dean Bryant, Cornelia Blume, Donna E. Davies, Emily J. Swindle
Summary: In this study, the researchers investigated the response of mast cells (MCs) to IL-33 stimulation and found that it increased the susceptibility of MCs to HRV infection through upregulation of ICAM1. This highlights a potential gene-environment interaction that could contribute to virus-induced asthma exacerbations.
Article
Cell Biology
Xinxuan Cheng, Danxue He, Chunyan Liao, Sijie Lin, Liying Tang, Yuan-Liang Wang, Jiaoyue Hu, Wei Li, Zuguo Liu, Yalin Wu, Yi Liao
Summary: The accumulation of all-trans-retinal (atRAL) has been proposed as a pathogenic factor in Stargardt disease type 1 (STGD1) and age-related macular degeneration (AMD). The study showed that atRAL induced complement activation through the alternative pathway in retinal pigment epithelium (RPE) cells, and led to the production of interleukin-1 beta. Inhibition of p38 and c-Jun N-terminal kinase (JNK) signaling pathways ameliorated complement activation in RPE cells, suggesting a potential therapeutic target for macular degeneration.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Anissa Fries, Fanny Saidoune, Francois Kuonen, Isabelle Dupanloup, Nadine Fournier, Ana Cristina Guerra de Souza, Muzlifah Haniffa, Feiyang Ma, Johann E. Gudjonsson, Lennart Roesner, Yang Li, Thomas Werfel, Curdin Conrad, Raphael Gottardo, Robert L. Modlin, Jeremy Di Domizio, Michel Gilliet
Summary: This study establishes the role of interleukin 26 (IL-26) in the generation of IL-17A producing Th17 CD4(+) T cells, indicating its involvement in the pathogenic response of psoriasis. IL-26-producing cells infiltrate psoriatic skin and promote their own differentiation into IL17A-producing T(H)17 cells through epithelial crosstalk involving paracrine production of TGF-& beta;1.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Olga Krysko, Darya Korsakova, Andrea Teufelberger, Amse De Meyer, Jill Steels, Natalie De Ruyck, Judith van Ovost, Sharon Van Nevel, Gabriele Holtappels, Frauke Coppieters, Mikhail Ivanchenko, Harald Braun, Maria Vedunova, Dmitri V. V. Krysko, Claus Bachert
Summary: This study found that there are differences in the number and protease content of lung mast cells between C57BL/6 and BALB/c mice, which may affect the processing of IL-33 and the inflammatory outcome of Alt-induced airway inflammation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Jikai Cui, Heng Xu, Jizhang Yu, Yuan Li, Zhang Chen, Yanqiang Zou, Xi Zhang, Yifan Du, Jiahong Xia, Jie Wu
Summary: Regulatory T cells differentiation is inhibited by IL-4 through epigenetic modulations. HDAC9 is involved in histone deacetylation process, affecting Foxp3 gene transcription, while sodium butyrate can abolish the inhibitory effects of IL-4.
CELL DEATH & DISEASE
(2021)
Article
Immunology
Sebastian Drube, Sylvia Mueller, Franziska Weber, Philine Wegner, Romy Boettcher-Loschinski, Matthias Gaestel, Andreas Hutloff, Thomas Kamradt, Nico Andreas
Summary: IL-33 activates multiple signaling pathways by binding to its receptor ST2, leading to the activation of different kinases and crucial for the production of IL-6 and IL-2. Unlike SCF, IL-3 can modulate the regulation of T-reg subpopulations by altering cytokine profiles, shifting the balance of T-regs induced by IL-33 towards a specific subset.
Article
Cell Biology
Nobuhiro Nakano, Jiro Kitaura
Summary: Mucosal mast cells (MMCs) in the intestinal mucosa play a crucial role in the development of IgE-mediated food allergies. Recent research has revealed that MMCs are distinct from connective tissue mast cells found in the skin and other tissues. The mechanism of MMC expansion and their cellular functions are not well understood. Research focusing on MMCs can provide valuable insights into the underlying mechanisms of food allergies and advance their treatment.
Review
Biochemistry & Molecular Biology
Matteo Trimarchi, Dorina Lauritano, Gianpaolo Ronconi, Alessandro Caraffa, Carla E. Gallenga, Ilias Frydas, Spyros K. Kritas, Vittorio Calvisi, Pio Conti
Summary: The etiopathogenesis of periodontal disease involves autoimmunity, inflammation affecting periodontal tissues and bone, and dysbiosis of oral microbiota triggering immune responses. Mast cells and cytokines play crucial roles in the inflammatory process in the gingiva.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Marcela T. Taruselli, Elizabeth Motunrayo Kolawole, Amina Abdul Qayum, Tamara T. Haque, Heather L. Caslin, Daniel Abebayehu, Sydney A. Kee, Jordan M. Dailey, Kaitlyn G. Jackson, Jason R. Burchett, Andrew J. Spence, Neha Pondicherry, Brian O. Barnstein, Gregorio Gomez, David B. Straus, John J. Ryan
Summary: This study found that fluvastatin enhances mast cell response to IL-33, promoting mast cell-mediated inflammatory reactions, and reveals the underlying mechanisms. These findings emphasize the importance of understanding the pleiotropic and potential unexpected effects of statins.
CELLULAR IMMUNOLOGY
(2022)
Article
Dermatology
Irene Lasheras-Otero, Iker Feliu, Alberto Maillo, Haritz Moreno, Marta Redondo-Munoz, Paula Aldaz, Ana Bocanegra, Ana Olias-Arjona, Fernando Lecanda, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Ignacio M. Larrayoz, David Gomez-Cabrero, Claudia Wellbrock, Silvestre Vicent, Imanol Arozarena
Summary: Circulating tumor cells play a crucial role in the development of distant metastases, but detachment in the bloodstream leads to cell death. A study found that melanoma circulating tumor cells increase lipid metabolism to survive by upregulating fatty acid transport and beta-oxidation-related genes. High expression of these genes in melanoma patients is associated with reduced survival. Targeting the interplay between peroxisomes and mitochondria in lipid metabolism could be a potential therapy for melanoma progression, with the FDA-approved drug ranolazine showing promise in inhibiting melanoma metastasis.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Jihye Kim, Yuliang He, Sabrina Tormen, Pascal Kleindienst, Luca Ducoli, Gaetana Restivo, Mathias Drach, Mitchell P. Levesque, Alexander A. Navarini, Carlotta Tacconi, Michael Detmar
Summary: This study found that fibroblasts isolated from psoriatic skin lesions maintain an abnormal phenotype even after several passages in culture. Transcriptomic analysis identified upregulated genes in psoriatic fibroblasts, including the extra domain A splice variant of fibronectin and ITGA4. Treatment with selective CBP/p300 inhibitors rescued the psoriatic fibroblast phenotype by reducing the expression levels of these genes. In a mouse model of psoriasis-like skin inflammation, systemic treatment with a potent CBP/p300 blocker reduced skin inflammation, immune cell recruitment, and inflammatory cytokine production. These findings suggest that epigenetic reprogramming could be a new approach for the treatment and prevention of psoriasis relapses.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Julia Lehmann, Nicole Caduff, Ewelina Krzywinska, Salome Stierli, Adrian Salas-Bastos, Benjamin Loos, Mitchell P. Levesque, Reinhard Dummer, Christian Stockmann, Christian Munz, Johanna Diener, Lukas Sommer
Summary: Metastatic melanoma, a leading cause of death in patients, can evade innate immune surveillance by expressing the stem cell marker NGFR, which down-regulates NK cell activating ligands and up-regulates the fatty acid SCD, promoting metastasis formation.
Article
Oncology
Ishani Banik, Adhideb Ghosh, Erin Beebe, Blaz Burja, Mojca Frank Bertoncelj, Christopher M. M. Dooley, Enni Markkanen, Reinhard Dummer, Elisabeth M. M. Busch-Nentwich, Mitchell P. P. Levesque
Summary: NRAS mutations are common in melanoma but lack targeted therapies. This study demonstrates that p38 acts as a tumor suppressor in NRAS mutant melanoma by regulating mTOR phosphorylation, autophagy, and actin remodeling. Pharmacologically available small molecules can modulate p38 and its downstream targets, providing a potential strategy for treating NRAS mutant melanoma. Combining these compounds with FDA-approved drugs like MEK inhibitors may offer a novel approach for targeting NRAS-mutant melanoma.
Article
Oncology
Ossia M. Eichhoff, Corinne I. Stoffel, Jan Kasler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pal Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque
Summary: The clinical management of NRAS-mutated melanomas is challenging due to resistance that arises through genetic, transcriptional, and metabolic adaptation. However, the adoption of a mesenchymal phenotype with a quiescent metabolic program in NRAS-mutated melanoma cells confers sensitivity to reactive oxygen species (ROS) induction, which can be inhibited by ROS inducers in combination with MAPK pathway inhibitors. The findings suggest that targeting both metabolic reprogramming and MAPK signaling could improve patient treatment in melanoma and other cancers.
Article
Oncology
Sara E. Cerminara, Phil Cheng, Lisa Kostner, Stephanie Huber, Michael Kunz, Julia-Tatjana Maul, Jette S. Bohm, Chiara F. Dettwiler, Anna Geser, Cecile Jakopovic, Livia M. Stoffel, Jelissa K. Peter, Mitchell Levesque, Alexander A. Navarini, Lara Valeska Maul
Summary: This study investigated the performance of 3D and 2D CNNs and dermatologists in early detection of melanoma. The 3D CNN outperformed the 2D CNN and achieved comparable sensitivity with dermatologists. Validating the classification of CNNs in real-life settings is emphasized.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Adriana Amaro, Francesco Reggiani, Daniela Fenoglio, Rosaria Gangemi, Anna Tosi, Alessia Parodi, Barbara Banelli, Valentina Rigo, Luca Mastracci, Federica Grillo, Alessandra Cereghetti, Aizhan Tastanova, Adhideb Ghosh, Fabio Sallustio, Laura Emionite, Antonio Daga, Tiziana Altosole, Gilberto Filaci, Antonio Rosato, Mitchell Levesque, Michele Maio, Ulrich Pfeffer, Michela Croce
Summary: The addition of Guadecitabine, an epigenetic drug, to immune checkpoint blockade therapy has shown promising results in treating malignant melanoma. It enhances the efficacy of the therapy by increasing immune cell activity and reducing tumor growth and metastasis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Dermatology
S. Steinmann, C. Guillet, P. F. Cheng, M. P. Levesque, R. Dummer, I. Kolm, J. T. Maul
Summary: This study retrospectively analyzed the pathological characteristics of 31 patients with primary cutaneous mucinoses and compared the differences between dermal and follicular mucin to determine their potential origins at the single-cell level. The results showed that mucin deposition in follicular mucinosis was exclusively found in hair follicles and sebaceous glands, while there was no mucin deposition in follicular epithelial structures of other entities. Multiplex fluorescence staining revealed that CD8+ T cells appeared to be more involved in mucin production in follicular mucinosis than in dermal mucinoses, which suggests that mucin in dermal and follicular epithelial mucinoses may have different origins.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mateusz S. Wietecha, David Lauenstein, Michael Cangkrama, Sybille Seiler, Juyoung Jin, Andreas Goppelt, Manfred Claassen, Mitchell P. Levesque, Reinhard Dummer, Sabine Werner
Summary: Healing wounds and cancers share similarities at the cellular and molecular levels. The specific roles of healing phases are poorly understood. By comparing gene expression patterns, it was found that a wound signature during the resolution phase is associated with more severe skin cancer. Comparison of early and late-phase wound fibroblasts with cancer-associated fibroblasts (CAFs) identified distinct subtypes of CAFs. These findings provide insights into wound-regulated genes and matrix patterns with prognostic potential in skin cancer.
Article
Medicine, Research & Experimental
Nicolas Gonzalo Nunez, Fiamma Berner, Ekaterina Friebel, Susanne Unger, Nina Wyss, Julia Martinez Gomez, Mette-Triin Purde, Rebekka Niederer, Maximilian Porsch, Christa Lichtensteiger, Rafaela Kramer, Michael Erdmann, Christina Schmitt, Lucie Heinzerling, Marie-Therese Abdou, Julia Karbach, Dirk Schadendorf, Lisa Zimmer, Selma Ugurel, Niklas Kluemper, Michael Hoelzel, Laura Power, Stefanie Kreutmair, Mariaelena Capone, Gabriele Madonna, Lacin Cevhertas, Anja Heider, Teresa Amaral, Omar Hasan Ali, David Bomze, Florentia Dimitriou, Stefan Diem, Paolo Antonio Ascierto, Reinhard Dummer, Elke Jaeger, Christoph Driessen, Mitchell Paul Levesque, Willem van de Veen, Markus Joerger, Martin Frueh, Burkhard Becher, Lukas Flatz
Summary: In this study, a multi-omics approach was used to characterize the systemic immune compartment of melanoma or non-small cell lung cancer patients before and during immune checkpoint inhibitor (ICI) treatment. Potential predictive biomarkers for ICI-induced immune-related adverse events (irAEs) were identified, including early increase in CXCL9/CXCL10/CXCL11 and interferon-g (IFN-g) 1 to 2 weeks after treatment initiation, as well as early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells.
Article
Oncology
Fabienne Frohlich, Egle Ramelyte, Patrick Turko, Andreas Dzung, Sandra N. Freiberger, Joanna Mangana, Mitchell P. Levesque, Reinhard Dummer
Summary: Although immunotherapy and targeted therapy have improved melanoma survival, some patients rapidly progress and decease within months after a stage IV diagnosis. This study aimed to find genetic alterations that predict short or long survival in melanoma patients and found that a clock-like mutational signature was associated with poor survival, while a UV mutational signature was prognostic for longer survival. These findings suggest that mutational signatures could be valuable prognostic markers for melanoma.
Article
Biology
Ulrike Lischetti, Aizhan Tastanova, Franziska Singer, Linda Grob, Matteo Carrara, Phil F. F. Cheng, Julia M. Martinez M. Gomez, Federica Sella, Veronika Haunerdinger, Christian Beisel, Mitchell P. Levesque
Summary: CITE-seq technology bridges the gap between RNA and protein in single-cell analysis, but its application to solid biopsies is limited. Applying CITE-seq to clinically relevant solid biopsies is an essential step in single-cell translational studies.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemical Research Methods
Evelyn Lattmann, Valerie Lapaire, Mitchell P. Levesque
Summary: This article describes a method for isolating and concentrating extracellular vesicles (EVs) from patient material, which can be used for studying and understanding diseases such as melanoma. Additionally, a protocol for analyzing the EVs using nano-flow cytometry is provided, and the obtained EV suspensions can be used for various downstream analyses including RNA sequencing and proteomics.
Meeting Abstract
Oncology
Haley P. Wilson, Timothy J. Purwin, Claudia Capparelli, Phil F. Cheng, Mitch P. Levesque, Reinhard Dummer, Jessica Teh, Andrew E. Aplin
Article
Biochemical Research Methods
Linda Grob, Anne Bertolini, Matteo Carrara, Ulrike Lischetti, Aizhan Tastanova, Christian Beisel, Mitchell P. Levesque, Daniel J. Stekhoven, Franziska Singer
Summary: Recently, a new single-cell technology called CITE-seq has emerged, which can capture both gene expression and surface protein information from individual cells. This technology provides unprecedented insights into disease mechanisms, heterogeneity, and immune cell profiling. However, most existing single-cell profiling methods focus on either gene expression or antibody analysis, not both. In addition, current software suites are not easily scalable for analyzing multiple samples. To address these challenges, we developed gExcite, a comprehensive workflow that enables gene and antibody expression analysis as well as hashing deconvolution. Embedded in the Snakemake workflow manager, gExcite ensures reproducibility and scalability. We demonstrate the output of gExcite using a study of different dissociation protocols on PBMC samples.