Article
Multidisciplinary Sciences
Qian Wang, Chenqi Tao, Abdul Hannan, Sungtae Yoon, Xuanyu Min, John Peregrin, Xiuxia Qu, Hongge Li, Honglian Yu, Jean Zhao, Xin Zhang
Summary: The patterning of epithelial buds in lacrimal gland development is determined by the interplay between PI3K, Ras, and ERK signaling pathways. PI3K is activated by both IGF and FGF signaling, and also promotes ERK signaling through direct interaction with Ras. Inhibition of EGF signaling is essential for induction of lacrimal gland buds, and the cross-talk among FGF, IGF, and EGF signaling is mediated by PI3K, MAPK, and mTOR.
Article
Plant Sciences
Mariko Kato, Machiko Watari, Tomohiko Tsuge, Sheng Zhong, Hongya Gu, Li-Jia Qu, Takashi Fujiwara, Takashi Aoyama
Summary: Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) and its product PtdIns(4,5)P-2 play a crucial role in pollen germination, possibly by establishing germination polarity in pollen.
Article
Multidisciplinary Sciences
Alessandro Poli, Shidqiyyah Abdul-Hamid, Antonio Enrico Zaurito, Francesca Campagnoli, Valeria Bevilacqua, Bhavwanti Sheth, Roberta Fiume, Massimiliano Pagani, Sergio Abrignani, Nullin Divecha
Summary: Regulatory T cells (Tregs) are crucial in maintaining peripheral tolerance and preventing autoimmunity, but their recruitment in tumor microenvironments can suppress immune surveillance. Pharmacological inhibition of PIP4K can reprogram human Treg identity without significantly impacting T conventional cell signaling, potentially improving therapeutic outcomes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Hema Adhikari, Walaa E. Kattan, Shivesh Kumar, Pei Zhou, John F. Hancock, Christopher M. Counter
Summary: The lipid composition of the plasma membrane plays a crucial role in defining the oncogenic function of KRAS, with the adapter protein EFR3A binding to active KRAS to recruit PI4KA and alter lipid composition. Disruption of EFR3A or PI4KA reduces oncogenic signaling and tumorigenesis, suggesting a potential therapeutic strategy for KRAS-mutant cancers.
NATURE COMMUNICATIONS
(2021)
Article
Plant Sciences
Machiko Watari, Mariko Kato, Romain Blanc-Mathieu, Tomohiko Tsuge, Hiroyuki Ogata, Takashi Aoyama
Summary: Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) is involved in regulating cellular processes. The study analyzed the functions of PIP5K genes in Arabidopsis and found different functions and promoter activities among PIP5K1, PIP5K2, and PIP5K3.
PLANT AND CELL PHYSIOLOGY
(2022)
Article
Plant Sciences
Ryo Kuroda, Mariko Kato, Tomohiko Tsuge, Takashi Aoyama
Summary: This study investigated the biological functions of the PIP5K7-9 subgroup genes in Arabidopsis thaliana, revealing their preferential expression in specific tissues and plasma membrane localization in root meristem cells. The genes were found to be redundant in adapting root growth to hyperosmotic conditions, possibly through promoting plasma membrane recycling in root meristem cells.
Article
Clinical Neurology
Hormos Salimi Dafsari, Joshua G. Pemberton, Elizabeth A. Ferrer, Tony Yammine, Chantal Farra, Mohammad Hasan Mohammadi, Ehsan Ghayoor Karimiani, Narges Hashemi, Mirna Souaid, Sandra Sabbagh, Paria Najarzadeh Torbati, Suliman Khan, Emmanuel Roze, Andres Moreno-De-Luca, Aida M. Bertoli-Avella, Henry Houlden, Tamas Balla, Reza Maroofian
Summary: This study describes the clinical presentation of patients with PI4K2A deficiency and explores the pathogenic mechanism. Cellular assays confirmed the deleterious effect of identified variants on PI4K2A activity and establish a link between late endosome-lysosome defects and neurodevelopmental disorders.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Wonyul Jang, Dmytro Puchkov, Paula Samso, YongTian Liang, Michal Nadler-Holly, Stephan J. Sigrist, Ulrich Kintscher, Fan Liu, Kamel Mamchaoui, Vincent Mouly, Volker Haucke
Summary: Cells respond to fluctuating nutrient supply by changing organelle dynamics and metabolism. This study reveals that lipid signaling on the endoplasmic reticulum can control mitochondrial morphology and function, enabling cells to adapt to changing nutrient environments.
Article
Plant Sciences
Nargis Parvin Laha, Ricardo F. H. Giehl, Esther Riemer, Danye Qiu, Naga Jyothi Pullagurla, Robin Schneider, Yashika Walia Dhir, Ranjana Yadav, Yeshambel Emewodih Mihiret, Philipp Gaugler, Verena Gaugler, Haibin Mao, Ning Zheng, Nicolaus von Wiren, Adolfo Saiardi, Saikat Bhattacharjee, Henning J. Jessen, Debabrata Laha, Gabriel Schaaf
Summary: This study reveals the critical role of ITPK1 in various auxin-related processes in plants. It interacts with the auxin receptor complex and generates specific inositol polyphosphates to modulate auxin perception and responses.
Article
Biochemistry & Molecular Biology
Sasja Blokzijl-Franke, Bas Ponsioen, Stefan Schulte-Merker, Philippe Herbomel, Karima Kissa, Suma Choorapoikayil, Jeroen den Hertog
Summary: The study found that HSPCs in mutant zebrafish embryos lacking pten function exhibited death during development, which could be rescued by inhibiting PI3K, while inhibiting PI3K in wild-type embryos also induced HSPC death. PI3K signaling tightly controls HSPC survival, with both up- and downregulation of the signaling pathway reducing stemness of HSPCs.
Article
Fisheries
Yunpeng Cao, Tao Fang, Yongxin Du, Ranting Li, Mingli Fan, Fei Ma, Ping Jin
Summary: This study identified a new member of the PIP5K family, AmphiPIP5K, in Cephalochordata and found its involvement in the innate immune response of amphioxus. The study also demonstrated that miR-2013 negatively regulates the expression of AmphiPIP5K to modulate the immune response in amphioxus.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2022)
Article
Cell Biology
Zhenzhen Guo, Chao-Hua Jiang, Chunfang Tong, Yanrui Yang, Zehua Wang, Sin Man Lam, Dou Wang, Rui Li, Guanghou Shui, Yun Stone Shi, Jia-Jia Liu
Summary: This study reveals the important role of phosphatidylinositol 4-phosphate (PI4P) in neuronal function, particularly in synaptic plasticity. The levels of PI4P increase significantly during long-term synaptic potentiation (LTP), and inhibition of PI4KIII alpha activity during LTP induction impairs LTP and long-term memory.
Article
Medicine, Research & Experimental
Hasibur Rehman, Darshan S. Chandrashekar, Chakravarthi Balabhadrapatruni, Saroj Nepal, Sai Akshaya Hodigere Balasubramanya, Abigail K. Shelton, Kasey R. Skinner, Ai-Hong Ma, Ting Rao, Sumit Agarwal, Marie-Lisa Eich, Alyncia D. Robinson, Gurudatta Naik, Upender Manne, George J. Netto, C. Ryan Miller, Chong-Xian Pan, Guru Sonpavde, Sooryanarayana Varambally, James E. Ferguson
Summary: The study reveals that bladder cancers with ARID1A mutations are more sensitive to EZH2 inhibitors and/or PI3K inhibitors. Mechanistic studies demonstrate that ARID1A deficiency leads to a dependency on PI3K signaling, and EZH2 inhibitor sensitivity is associated with upregulation of PIK3IP1. Moreover, combination therapy with EZH2 and PI3K inhibitors shows a synergistic effect on ARID1A-deficient bladder cancer.
Article
Plant Sciences
Jeong Hun Kim, Hyera Jung, Kyoungjun Song, Han Nim Lee, Taijoon Chung
Summary: Phosphatidylinositol 3-phosphate (PI3P) is a signaling phospholipid that is crucial for endomembrane trafficking, including autophagy and endosomal trafficking. The role of PI3P downstream effectors in plant autophagy, particularly regarding ATG18A and FYVE2, has been unclear. In this study, we demonstrate that FYVE3, a paralog of plant-specific FYVE2, interacts with ATG18A and FYVE2 and contributes to autophagy regulation. FYVE3 is transported to the vacuole and its delivery relies on PI3P biosynthesis and the canonical autophagic machinery. The fyve3 mutation suppresses defective autophagy in fyve2 mutants, suggesting a specific role of FYVE3 in FYVE2-dependent autophagy.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Medicine, General & Internal
Shuhong Yin, Xiuying Lin
Summary: The study found that miR-21 is up-regulated in CSCC tissues, while TIMP3 is down-regulated, and this is associated with poor survival in patients. Depletion of miR-21 impedes CSCC cell invasion and metastasis by enhancing TIMP3 and suppressing PI3K/AKT pathway activation.
INTERNATIONAL JOURNAL OF GENERAL MEDICINE
(2021)
Article
Immunology
Cinzia Fionda, Helena Stabile, Rosa Molfetta, Andrea Kosta, Giovanna Peruzzi, Silvia Ruggeri, Alessandra Zingoni, Cristina Capuano, Alessandra Soriani, Rossella Paolini, Angela Gismondi, Marco Cippitelli, Angela Santoni
Summary: The protein CRBN plays a critical role in regulating NK cell functions, including cytoskeleton rearrangement, cytotoxicity, and migration. CRBN depletion leads to reduced cytotoxicity, impairment of synapse formation, and decreased migration ability in NK cells. Additionally, CRBN is involved in the activation of Rac1, a key mediator of cytoskeleton dynamics.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Chiara Di Censo, Marie Marotel, Irene Mattiola, Lena Mueler, Gianluca Scarno, Giuseppe Pietropaolo, Giovanna Peruzzi, Mattia Laffranchi, Julija Mazej, Mohamed Shaad Hasim, Sara Asif, Eleonora Russo, Luana Tomaipitinca, Helena Stabile, Seung-Hwan Lee, Laura Vian, Massimo Gadina, Angela Gismondi, Han-Yu Shih, Yohei Mikami, Cristina Capuano, Giovanni Bernardini, Michael Bonelli, Silvano Sozzani, Andreas Diefenbach, Michele Ardolino, Angela Santoni, Giuseppe Sciume
Summary: Liver ILC1 exhibit heterogeneity in the expression of distinct effector molecules and surface receptors, with a subset expressing high levels of granzyme A enriched in adult mice. The heterogeneity of GzmA and CD160 expression in hepatic ILC1 begins perinatally and increases with age. ILC1 characterized by the expression of GzmA and CD160 show graded cytotoxic potential and ability to produce IFN-gamma, indicating functional diversification.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Cell Biology
Sara Petillo, Cristina Capuano, Rosa Molfetta, Cinzia Fionda, Abdelilah Mekhloufi, Chiara Pighi, Fabrizio Antonangeli, Alessandra Zingoni, Alessandra Soriani, Maria Teresa Petrucci, Ricciarda Galandrini, Rossella Paolini, Angela Santoni, Marco Cippitelli
Summary: In this study, it was found that inhibition of neddylation using MLN4924/Pevonedistat can increase the expression of NK cell-activating ligands on the plasma membrane of MM cells, leading to enhanced NK cell degranulation. This suggests that modulation of neddylation can sensitize MM to NK cell killing, providing new insights into the anticancer activity of neddylation inhibition.
CELL DEATH & DISEASE
(2021)
Review
Oncology
Cristina Capuano, Chiara Pighi, Simone Battella, Davide De Federicis, Ricciarda Galandrini, Gabriella Palmieri
Summary: NK cells play a crucial role in cancer immunotherapy based on tumor-targeting monoclonal antibodies by interacting with IgG-opsonized tumor cells through the CD16 receptor. Activated NK cells not only exert cytotoxic functions but also produce a range of cytokines and chemokines to enhance adaptive immune responses. Strategies aiming to enhance NK cell-mediated antitumor functions in tumor-targeting monoclonal antibody regimens include mAb manipulation strategies and the potential exploitation of memory NK cells with unique characteristics.
Review
Immunology
Martina Kunkl, Carola Amormino, Valentina Tedeschi, Maria Teresa Fiorillo, Loretta Tuosto
Summary: This review summarizes the changes and behavior of astrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis, as well as the contribution of pathogenic T cell subsets and CD8(+) T cells to astrocytic modifications and pathological outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Benedetta Mattorre, Silvana Caristi, Simona Donato, Emilia Volpe, Marika Faiella, Alessandro Paiardini, Rosa Sorrentino, Fabiana Paladini
Summary: The common expression of ERAP1 and IRAP in humans, as well as the evolution of ERAP2 under balancing selection leading to the generation of a short form, suggest a significant yet debated role of these metalloproteases in antigen presentation and other cellular processes, as evidenced by their complex interactions in macrophages and some cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Valentina Tedeschi, Giorgia Paldino, Martina Kunkl, Marino Paroli, Rosa Sorrentino, Loretta Tuosto, Maria Teresa Fiorillo
Summary: CD8(+) T lymphocytes play a crucial role in immune response, but aging and disease can alter their function and phenotype, impacting vaccine and treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Cristina Capuano, Chiara Pighi, Simone Battella, Fabio Pulcinelli, Cristina Santoro, Antonietta Ferretti, Ombretta Turriziani, Davide De Federicis, Cinzia Fionda, Giuseppe Sciume, Ricciarda Galandrini, Gabriella Palmieri
Summary: The in vivo establishment and long-term persistence of a heterogeneous memory or an adaptive NK cell pool play a functional adaptation role to human cytomegalovirus infection in humans. The FcεRIγ(-) NKG2C(+)CD57(+) memory NK cell subset, whose abundance is associated with anti-HCMV antibody levels, expands robustly and selectively in response to mAb-opsonized targets or ITP-derived platelets, demonstrating superior CD16-dependent IFNγ production. The lack of FcεRIγ chain contributes to the higher responsivity to CD16 engagement in NKG2C(+)CD57(+) memory cells.
Article
Cell Biology
Carola Amormino, Valentina Tedeschi, Giorgia Paldino, Stefano Arcieri, Maria Teresa Fiorillo, Alessandro Paiardini, Loretta Tuosto, Martina Kunkl
Summary: The SARS-CoV-2 spike protein does not exhibit superantigen-like activity, contradicting the superantigen theory of MIS-C.
Editorial Material
Immunology
Loretta Tuosto
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Nadia D. Milito, Alessandra Zingoni, Helena Stabile, Alessandra Soriani, Cristina Capuano, Marco Cippitelli, Angela Gismondi, Angela Santoni, Rossella Paolini, Rosa Molfetta
Summary: The activation of natural killer (NK) cells is influenced by activating and inhibitory receptors which aid in identifying diseased cells. Among these receptors, NKG2D and DNAM-1 are crucial for the immune response against cancer as they bind to ligands expressed on transformed cells. However, during tumor progression, these receptors are often downregulated and lose their functionality. NKG2D internalization has been associated with dysfunctional phenotype characterized by tolerance to other activating receptors. Nevertheless, the consequences of NKG2D engagement are still incompletely understood. In this study, we demonstrate that NKG2D engagement impairs DNAM-1-mediated killing on human NK cells through two converging mechanisms: upregulation of the inhibitory receptor TIGIT, which suppresses DNAM-1-mediated cytotoxic function, and direct inhibition of DNAM-1 signaling. These findings reveal a novel interplay between NKG2D and DNAM-1/TIGIT receptors that may enable neoplastic cells to evade clearance by NK cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Rheumatology
Lucia Novelli, Cristiana Barbati, Cristina Capuano, Serena Recalchi, Fulvia Ceccarelli, Marta Vomero, Cristiano Alessandri, Stefania Morrone, Fabrizio Conti
Summary: This study investigated the expression of KLRG1 in SLE patients compared to healthy controls on both NK and T cells, as well as its possible involvement in SLE pathogenesis. The results showed that KLRG1 expression was significantly reduced on immune cell populations in SLE patients, especially on total NK cells. In addition, KLRG1 expression on NK cells was inversely correlated with disease activity and associated with treatment with HCQ. In vitro treatment with HCQ increased KLRG1 expression on NK cells. These findings suggest a role of KLRG1 in the pathogenesis of SLE and its potential as a biomarker for this disease.
Article
Immunology
Martina Kunkl, Carola Amormino, Francesco Spallotta, Silvana Caristi, Maria Teresa Fiorillo, Alessandro Paiardini, Raymond Kaempfer, Loretta Tuosto
Summary: Staphylococcus aureus superantigens (SAgs) like staphylococcal enterotoxin A (SEA) and B (SEB) can cause toxic shock and sepsis by stimulating T cells to produce excessive inflammatory cytokines. Using an AI-based algorithm, we have discovered a new mechanism of action for SAgs, showing that SEA and SEB can bind to TCR and CD28 independently of MHC class II- and B7-expressing antigen presenting cells, leading to inflammatory signal activation and massive cytokine secretion.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Valentina Tedeschi, Giorgia Paldino, Josephine Alba, Emanuele Molteni, Fabiana Paladini, Rossana Scrivo, Mattia Congia, Alberto Cauli, Rosalba Caccavale, Marino Paroli, Manuela Di Franco, Loretta Tuosto, Rosa Sorrentino, Marco D'Abramo, Maria Teresa Fiorillo
Summary: The HLA-B*27 family of alleles is strongly associated with ankylosing spondylitis (AS), but some non-associated HLA-B*27 variants have been found. The quantity of presented epitopes, rather than the quality, may explain the difference. The ERAP1/2 haplotype and the B*27:05 allele play crucial roles in shaping the CD8+ T cell response to viral and self-B*27 peptides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Immunology
Martina Kunkl, Carola Amormino, Simone Frascolla, Manolo Sambucci, Marco De Bardi, Silvana Caristi, Stefano Arcieri, Luca Battistini, Loretta Tuosto
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)