Article
Multidisciplinary Sciences
Scott Frendo-Cumbo, Taoyingnan Li, Dustin A. Ammendolia, Etienne Coyaud, Estelle M. N. Laurent, Yuan Liu, Philip J. Bilan, Gordon Polevoy, Brian Raught, Julie A. Brill, Amira Klip, John H. Brumell
Summary: Cell proliferation is regulated by growth factors insulin and IGF1. The study identified DCAF7 as an interactor of IRS1, a mediator of insulin/IGF1 signaling, that regulates cell proliferation and cell cycle through the IRS1-FOXO1 signaling pathway. DCAF7 knockdown led to cell cycle arrest and reduced cell proliferation.
Article
Biochemistry & Molecular Biology
Guang-Liang Chen, Rui Li, Xiao-Xiang Chen, Juan Wang, Shan Cao, Rui Song, Ming-Chun Zhao, Li-Ming Li, Nicole Hannemmann, Georg Schett, Cheng Qian, Aline Bozec
Summary: Metastatic melanoma is a challenging disease, and understanding the molecular mechanisms behind its metastasis is crucial. The downregulation of AP-1 transcription factor member Fra-2 in melanoma cells is associated with a more aggressive phenotype both in vitro and in vivo. Further research revealed that the Fra-2-Fam212b axis plays a key role in promoting melanoma metastasis by affecting cell migration, invasion, cell cycle transition, and tissue angiogenesis.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Medicine, Research & Experimental
Rahul S. Bhansali, Malini Rammohan, Paul Lee, Anouchka P. Laurent, Qiang Wen, Praveen Suraneni, Bon Ham Yip, Yi-Chien Tsai, Silvia Jenni, Beat Bornhauser, Aurelie Siret, Corinne Fruit, Alexandra Pacheco-Benichou, Ethan Harris, Thierry Besson, Benjamin J. Thompson, Young Ah Goo, Nobuko Hijiya, Maria Vilenchik, Shai Izraeli, Jean-Pierre Bourquin, Sebastien Malinge, John D. Crispino
Summary: The study reveals that DYRK1A is overexpressed in and essential for B-ALL, with FOXO1 and STAT3 being critical substrates. Loss of DYRK1A-mediated FOXO1 and STAT3 signaling disrupts DNA damage and ROS regulation, leading to preferential cell death in leukemic B cells.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Immunology
Diana Schnoegl, Mathias Hochgerner, Dagmar Gotthardt, Leigh M. Marsh
Summary: NK cell deficiency caused by aberrant expression of the transcription factor Fra-2 is associated with pulmonary fibrosis and inflammation in systemic sclerosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Sarah L. Cook, Evelyn P. Sievert, Roger Sciammas
Summary: The transcription factor IRF4 is essential for the selection of high-affinity GCBs, with halving Irf4 gene copy number leading to impaired generation of high-affinity cells. This study highlights the continuous role of IRF4 in later phases of the B cell response, promoting productive T follicular helper cell interactions and optimal Blimp-1 expression during GC selection and affinity maturation.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yongguang Zhang, Dongya Cui, Miaohui Huang, Yongwei Zheng, Baijiao Zheng, Liling Chen, Qi Chen
Summary: The protein NONO is a multifunctional nuclear protein that regulates transcriptional regulation, mRNA splicing, and DNA repair. This study shows that NONO has a critical role in B-cell development and B-cell activation. Deletion of NONO impairs early B-cell development and B-cell maturation, as well as the activation of pathways involved in B-cell activation, such as ERK, AKT, and NF-kappa B.
Article
Immunology
Kristina Ottens, Anne B. Satterthwaite
Summary: Strict control of B lymphocyte development is crucial for mounting immune responses effectively while maintaining self-tolerance.One of the key transcription factors, IRF4, plays a significant role in regulating different developmental stages and subtypes of B cells. Its unique functions range from limiting marginal zone B cell development to promoting plasma cell differentiation, highlighting its dominant role in early B lymphopoiesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Arnaud Delpoux, Nimi Marcel, Rodrigo Hess Michelini, Carol D. Katayama, Karmel A. Allison, Christopher K. Glass, Sergio M. Quinones-Parra, Cornelis Murre, Liyen Loh, Katherine Kedzierska, Martha Lappas, Stephen M. Hedrick, Andrew L. Doedens
Summary: This study demonstrates the crucial role of FOXO1 in maintaining cellular vitality and response to antigenic stress in T cells. Different cellular age states may lead to alterations in levels of FOXO1, TCF7, and AP-1 factors. These characteristics are also associated with the formation of T cells with features of cellular senescence.
Review
Medicine, Research & Experimental
Rossana Maffei, Stefania Fiorcari, Claudio Giacinto Atene, Silvia Martinelli, Nicolo Mesini, Flora Pilato, Ivana Lagreca, Patrizia Barozzi, Giovanni Riva, Vincenzo Nasillo, Ambra Paolini, Fabio Forghieri, Leonardo Potenza, Tommaso Trenti, Enrico Tagliafico, Mario Luppi, Roberto Marasca
Summary: Interferon regulatory factor 4 (IRF4) plays a crucial role in regulating B cell development and is associated with B cell malignancies. The complexity of IRF4 functions includes its involvement in different DNA-binding affinity, target motifs, and transcriptional partners.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Limin Shi, Zhipeng Tao, Louise Zheng, Jinying Yang, Xinran Hu, Karen Scott, Annette de Kloet, Eric Krause, James F. Collins, Zhiyong Cheng
Summary: The transcription factor FoxO1 regulates adipose transdifferentiation by mediating Tgf beta 1 signaling. Loss of FoxO1 induces browning of adipose tissue and increases energy expenditure. The FoxO1-Tgf beta 1 signaling cascade also plays a role in adipose browning induced by beta 3-AR agonist.
Article
Immunology
Romane Thouenon, Loic Chentout, Nidia Moreno-Corona, Lucie Poggi, Emilia Puig Lombardi, Benedicte Hoareau, Yohann Schmitt, Chantal Lagresle-Peyrou, Jacinta Bustamante, Isabelle Andre, Marina Cavazzana, Anne Durandy, Jean-Laurent Casanova, Lionel Galicier, Jehane Fadlallah, Alain Fischer, Sven Kracker
Summary: Thouenon et al. have described a novel primary immunodeficiency caused by disrupted plasma cell differentiation. They found that a specific amino acid exchange in the interferon activation domain of IRF4 results in reduced transcription on ISRE sites due to altered protein interaction. In this study, a heterozygous missense variant in the IRF4 gene was identified in three patients with hypogammaglobulinemia. The mutant IRF4 protein was shown to decrease the expression of key transcription factors involved in plasma cell differentiation and displayed impaired transcriptional activity on ISREs. This study provides insights into the mechanism of autosomal-dominant primary immunodeficiency and its impact on plasma cell differentiation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Cell Biology
Fan Wu, Chunlin Li
Summary: This study investigated the role of Kruppel-like factor 2 (KLF2) and its downstream molecular mechanism in neonatal brain hypoxic ischemic injury. Results showed that overexpression of KLF2 inhibited neuron apoptosis and alleviated brain injury.
CELL DEATH DISCOVERY
(2022)
Article
Immunology
Jaya Prakash Chalise, Ali Ehsani, Mengistu Lemecha, Yu-Wen Hung, Guoxiang Zhang, Garrett P. Larson, Keiichi Itakura
Summary: During B-cell development, dysregulation of ARID5B expression can lead to the failure of producing functional B cells, increasing the risk of B-cell leukemia. In mice and humans, ARID5B is upregulated during the Pre-B stage and continues to be expressed in later stages of B-cell development. Deletion of Arid5b in mice resulted in a reduction of immature B cells but an increase in large and small Pre-B cells. It was also found that ARID5B regulates fatty acid metabolism and affects the proliferation of Pre-B cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Olivier Papapietro, Sergey Nejentsev
Summary: TOP2B plays a crucial role in transcription regulation and maintaining genome organization by unwinding DNA structures. Deficiency of TOP2B may lead to developmental defects in B-cell progenitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Developmental Biology
Shizheng Zhao, Ao Zhang, Hao Zhu, Zilong Wen
Summary: The study reports the identification and characterization of a new member of the ETS transcription factors, Spi2, in ray-finned fish. It shows that Spi2 is crucial for hematopoietic stem and progenitor cell development and myeloid lineage differentiation. A reporter line is created to track these cells from early development to adulthood.
Article
Rheumatology
Laura C. Coates, Laure Gossec, Elke Theander, Paul Bergmans, Marlies Neuhold, Chetan S. Karyekar, May Shawi, Wim Noel, Georg Schett, Iain B. McInnes
Summary: The study demonstrated that guselkumab significantly improved joint and skin manifestations as well as physical function in patients with TNFi-IR PsA. A higher proportion of patients in the guselkumab group achieved ACR20 and other key secondary endpoints compared to the placebo group, with 58% of ACR20 response in the guselkumab group at week 48.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Letter
Rheumatology
Klara Martinsson, Kerstin Durholz, Georg Schett, Mario M. Zaiss, Alf Kastbom
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Review
Rheumatology
Enrico De Lorenzis, Gerlando Natalello, David Simon, Georg Schett, Maria Antonietta D'Agostino
Summary: Pain is the main symptom in entheseal diseases. Eicosanoids, cytokines, and neuropeptides released during inflammation and mechanical challenge stimulate nerves and blood vessels to invade the enthesis. Nociceptive pseudounipolar neurons support this process by releasing neurotransmitters that induce neovascularization and sensitization, which may explain the dissociation between pain and imaging findings.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Endocrinology & Metabolism
Chaobo Lai, Jennifer Heinemann, Ulrike Schleicher, Georg Schett, Christian Bogdan, Aline Bozec, Didier Soulat
Summary: Chronic infection with Leishmania increases bone mass by inducing bone formation and impairing osteoclast differentiation and function.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Rheumatology
Merlijn H. Kaaij, Jan Piet van Hamburg, Charlotte C. N. van Rooijen, Anika Grueneboom, Yik Y. Kan, Desiree Pots, Georg Schett, Leo J. van Ruijven, Leonie M. van Duivenvoorde, Leonie F. A. Huitema, Dominique L. P. Baeten, Sander W. Tas
Summary: This study found that the increase of type H vessels in a transgenic mouse model is closely related to pathologic osteogenesis. This finding provides new insights into the pathophysiology of ankylosing spondylitis and may offer a novel target for intervention.
ARTHRITIS & RHEUMATOLOGY
(2023)
Editorial Material
Rheumatology
Larissa Valor-Mendez, Armin Atzinger, Petra Reis, Bernhard Manger, Georg Schett
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Rheumatology
David Simon, Ioanna Minopoulou, Stephan Kemenes, Sara Bayat, Koray Tascilar, Melek Yalcin Mutlu, Larissa Valor-Mendez, Gerhard Kroenke, Axel J. Hueber, Georg Schett, Arnd Kleyer
Summary: Objective. This study aimed to evaluate the effect of Janus kinase inhibition (JAKi) through baricitinib (BARI) on bone properties and synovial inflammation in rheumatoid arthritis (RA) patients. Results showed that BARI therapy significantly improved disease activity, synovial inflammation, and bone mass of RA patients, with no new safety signals observed.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Rheumatology
Xiang Zhou, Thuong Trinh-Minh, Alexandru-Emil Matei, Andrea-Hermina Gyoerfi, Xuezhi Hong, Christina Bergmann, Georg Schett, John Atkinson, Rowann Bowcutt, Jessal Patel, Timothy S. Johnson, Joerg H. W. Distler
Summary: In this study, increased expression and activity of TG2 were observed in systemic sclerosis (SSc) patients. Inhibition of TG2 in dermal fibroblasts resulted in reduced fibrosis, suggesting that targeting TG2 may be a potential antifibrotic approach in SSc.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Rheumatology
Dennis McGonagle, Iain B. B. McInnes, Atul Deodhar, Georg Schett, May Shawi, Soumya D. D. Chakravarty, Alexa P. P. Kollmeier, Xie L. L. Xu, Shihong Sheng, Stephen Xu, Christopher T. T. Ritchlin, Proton Rahman, Phillip J. J. Mease
Summary: The study found that a higher proportion of patients treated with guselkumab achieved resolution of dactylitis, and this resolution was associated with other important clinical outcomes.
ACR OPEN RHEUMATOLOGY
(2023)
Article
Endocrinology & Metabolism
Stefan Bartenschlager, Alexander Cavallaro, Tobias Pogarell, Oliver Chaudry, Michael Uder, Sundeep Khosla, Georg Schett, Klaus Engelke
Summary: Opportunistic screening is a promising technique for identifying individuals at high risk for osteoporotic fracture using CT scans. This study compared the performance of four existing phantomless calibration methods and found that precalibrated phantomless calibration methods performed well.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Review
Rheumatology
James Brock, Neil Basu, Johannes C. M. Schlachetzki, Georg Schett, Iain B. Mcinnes, Jonathan Cavanagh
Summary: Depression is a common comorbidity in rheumatoid arthritis, and shared immune mechanisms link the two conditions. This Review explores potential peripheral and central interactions between the immune system and brain, the understanding of which could aid in the development of novel therapeutics.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Rheumatology
Daniele Mauro, Saviana Gandolfo, Enrico Tirri, Georg Schett, Walter P. P. Maksymowych, Francesco Ciccia
Summary: This perspective discusses the evidence that supports a bone marrow origin for spondyloarthritis, rather than an entheseal origin. Focusing on immune cells and dysfunction in the bone marrow niche could alter the therapeutic approach to spondyloarthritis.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Rheumatology
Georg Schett, Warner Chen, Sheng Gao, Soumya D. Chakravarty, May Shawi, Frederic Lavie, Miriam Zimmermann, Mohamed Sharaf, Laura C. Coates, Stefan Siebert
Summary: In the COSMOS trial, guselkumab demonstrated efficacy in treating TNFi-IR PsA patients by reducing levels of effector cytokines associated with the IL-23/IL-17 pathway.
ARTHRITIS RESEARCH & THERAPY
(2023)
Article
Rheumatology
Sophie von Rohr, Johannes Knitza, Manuel Grahammer, Marc Schmalzing, Sebastian Kuhn, Georg Schett, Andreas Ramming, Hannah Labinsky
Summary: The study aimed to investigate the use of student-led clinics and electronic patient-reported outcomes (ePROs) for the diagnosis and treatment of patients with axial spondyloarthritis (axSpA). The results showed that student-led clinics significantly accelerated patient appointments and NSAID therapy start, and completed the diagnostic workup for all patients. The electronic and paper-administered BASDAI questionnaires showed good correlation. Both student-led clinics and ePRO monitoring were well accepted by patients.
RHEUMATOLOGY INTERNATIONAL
(2023)
Article
Rheumatology
Hannah Labinsky, Latika Gupta, Maria Gabriella Raimondo, Georg Schett, Johannes Knitza
Summary: Mobile health applications and digital therapeutics aim to improve patient care, but real-world data on their efficacy is scarce. This study evaluated the adherence, acceptance, and efficacy of digital therapeutics in a rheumatology setting. Results showed high acceptance of digital therapeutics in rheumatic disease patients, but challenges in onboarding and adherence were observed. A subgroup of patients using exercise-based digital therapeutics reported symptom improvement.
RHEUMATOLOGY INTERNATIONAL
(2023)