المؤلفون: Singh P; Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary., Száraz-Széles M; Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary., Baráth S; Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary., Hevessy Z; Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 May 28; Vol. 25 (11). Date of Electronic Publication: 2024 May 28.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

مواضيع طبية MeSH: Mucosal-Associated Invariant T Cells*/immunology , Mucosal-Associated Invariant T Cells*/metabolism , Mucosal-Associated Invariant T Cells*/drug effects , NK Cell Lectin-Like Receptor Subfamily B*/metabolism, Humans ; Lymphocyte Activation/drug effects ; Lymphocyte Activation/immunology ; Immunologic Factors/pharmacology ; Cytokines/metabolism ; Cyclosporine/pharmacology ; Cholecalciferol/pharmacology ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/immunology

مستخلص: Mucosal-associated invariant T (MAIT) cells, a subset of Vα7.2+ T cells, are a crucial link between innate and adaptive immunity, responding to various stimuli through TCR-dependent and independent pathways. We investigated the responses of MAIT cells and Vα7.2+/CD161- T cells to different stimuli and evaluated the effects of Cyclosporin A (CsA) and Vitamin D3 (VitD). Peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with various agents (PMA/Ionomycin, 5-OP-RU, 5-OP-RU/IL-12/IL-33) with or without CsA and VitD. Flow cytometric analysis assessed surface markers and intracellular cytokine production. Under steady-state conditions, MAIT cells displayed elevated expression of CCR6 and IL-13. They showed upregulated activation and exhaustion markers after activation, producing IFNγ, TNFα, and TNFα/GzB. CsA significantly inhibited MAIT cell activation and cytokine production. Conversely, Vα7.2+/CD161- T cells exhibited distinct responses, showing negligible responses to 5-OP-RU ligand but increased cytokine production upon PMA stimulation. Our study underscores the distinct nature of MAIT cells compared to Vα7.2+/CD161- T cells, which resemble conventional T cells. CsA emerges as a potent immunosuppressive agent, inhibiting proinflammatory cytokine production in MAIT cells. At the same time, VitD supports MAIT cell activation and IL-13 production, shedding light on potential therapeutic avenues for immune modulation.

المؤلفون: Li M; Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Yu W; Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Liu Z; Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Liu S; Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 May 24; Vol. 25 (11). Date of Electronic Publication: 2024 May 24.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

مواضيع طبية MeSH: Psoriasis*/immunology , Psoriasis*/metabolism , Psoriasis*/pathology , Psoriasis*/chemically induced , Psoriasis*/genetics , Macrophages*/metabolism , Macrophages*/immunology , Skin*/metabolism , Skin*/pathology , Skin*/immunology , Sialic Acid Binding Ig-like Lectin 1*/metabolism , Imiquimod*, Animals ; Mice ; Cytokines/metabolism ; Disease Models, Animal ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Cell Differentiation ; Mice, Inbred C57BL

مستخلص: Skin macrophages are critical to maintain and restore skin homeostasis. They serve as major producers of cytokines and chemokines in the skin, participating in diverse biological processes such as wound healing and psoriasis. The heterogeneity and functional diversity of macrophage subpopulations endow them with multifaceted roles in psoriasis development. A distinct subpopulation of skin macrophages, characterized by high expression of CD169, has been reported to exist in both mouse and human skin. However, its role in psoriasis remains unknown. Here, we report that CD169 ⁺ macrophages exhibit increased abundance in imiquimod (IMQ) induced psoriasis-like skin lesions. Specific depletion of CD169 ⁺ macrophages in CD169-ditheria toxin receptor (CD169-DTR) mice inhibits IMQ-induced psoriasis, resulting in milder symptoms, diminished proinflammatory cytokine levels and reduced proportion of Th17 cells within the skin lesions. Furthermore, transcriptomic analysis uncovers enhanced activity in CD169 ⁺ macrophages when compared with CD169 ^- macrophages, characterized by upregulated genes that are associated with cell activation and cell metabolism. Mechanistically, CD169 ⁺ macrophages isolated from IMQ-induced skin lesions produce more proinflammatory cytokines and exhibit enhanced ability to promote Th17 cell differentiation in vitro. Collectively, our findings highlight the crucial involvement of CD169 ⁺ macrophages in psoriasis development and offer novel insights into the heterogeneity of skin macrophages in the context of psoriasis.

المؤلفون: You J; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China., Wang S; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China., Zhu Y; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China., Zhang Z; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China., Wang J; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China., Lou Y; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China., Yao Y; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China., Hao Y; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China., Liu P; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.

المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 May 09; Vol. 25 (10). Date of Electronic Publication: 2024 May 09.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

مواضيع طبية MeSH: Myeloid-Derived Suppressor Cells*/metabolism , Myeloid-Derived Suppressor Cells*/immunology , Killer Cells, Natural*/immunology , Killer Cells, Natural*/metabolism , NK Cell Lectin-Like Receptor Subfamily K*/metabolism , Tumor Necrosis Factor-alpha*/metabolism, Animals ; Mice ; Mice, Inbred C57BL ; Lymphocyte Activation/immunology ; Cell Differentiation ; Ligands ; ADAM17 Protein/metabolism

مستخلص: In our previous studies, a novel cryothermal therapy (CTT) was developed to induce systemic long-term anti-tumor immunity. Natural killer (NK) cells were found to play an important role in CTT-induced long-term immune-mediated tumor control at the late stage after CTT, but the underlying mechanism is unclear. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that have potent immunosuppressive effects on T cells and weaken the long-term benefits of immunotherapy. Consequently, overcoming MDSC immunosuppression is essential for maintaining the long-term efficacy of immunotherapy. In this study, we revealed that NK cells considerably diminish MDSC accumulation at the late stage after CTT, boost T cell production, increase T cell activation, and promote MDSC maturation, culminating in Th1-dominant CD4 ⁺ T cell differentiation and enhancing NK and CD8 ⁺ T cell cytotoxicity. Additionally, NK cells activate ERK signaling in MDSCs through NKG2D-ligand interaction to increase the activity of tumor necrosis factor (TNF)-α converting enzyme (TACE)-cleaved membrane TNF-α. Furthermore, Increased TACE activity releases more soluble TNF-α from MDSCs to promote MDSC maturation. In our studies, we propose a novel mechanism by which NK cells can overcome MDSC-induced immunosuppression and maintain CTT-induced persistent anti-tumor immunity, providing a prospective therapeutic option to improve the performance of cancer immunotherapy.

المؤلفون: Díaz-Tejedor A; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., Rodríguez-Ubreva J; Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), 08916 Badalona, Spain., Ciudad L; Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), 08916 Badalona, Spain., Lorenzo-Mohamed M; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., González-Rodríguez M; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., Castellanos B; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., Sotolongo-Ravelo J; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., San-Segundo L; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., Corchete LA; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.; Centro de Investigación Biomédica En Red de Cáncer (CIBERONC, CB16/12/00233), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain., González-Méndez L; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., Martín-Sánchez M; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., Mateos MV; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.; Centro de Investigación Biomédica En Red de Cáncer (CIBERONC, CB16/12/00233), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain.; Departamento de Medicina, Universidad de Salamanca, 37007 Salamanca, Spain., Ocio EM; Hospital Universitario Marqués de Valdecilla (IDIVAL), Universidad de Cantabria, 39008 Santander, Spain., Garayoa M; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain., Paíno T; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC), Universidad de Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007 Salamanca, Spain.; Servicio de Hematología, Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.; Centro de Investigación Biomédica En Red de Cáncer (CIBERONC, CB16/12/00233), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain.; Departamento de Fisiología y Farmacología, Universidad de Salamanca, 37007 Salamanca, Spain.

المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Apr 26; Vol. 25 (9). Date of Electronic Publication: 2024 Apr 26.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

مواضيع طبية MeSH: Multiple Myeloma*/drug therapy , Multiple Myeloma*/metabolism , Multiple Myeloma*/pathology , ADP-ribosyl Cyclase 1*/metabolism , ADP-ribosyl Cyclase 1*/antagonists & inhibitors , Antibodies, Monoclonal*/pharmacology , NK Cell Lectin-Like Receptor Subfamily K*/metabolism, Humans ; Animals ; Mice ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Membrane Glycoproteins/metabolism ; Drug Synergism ; Histocompatibility Antigens Class I/metabolism ; Histocompatibility Antigens Class I/genetics ; Up-Regulation/drug effects

مستخلص: Multiple myeloma is a malignancy characterized by the accumulation of malignant plasma cells in bone marrow and the production of monoclonal immunoglobulin. A hallmark of cancer is the evasion of immune surveillance. Histone deacetylase inhibitors have been shown to promote the expression of silenced molecules and hold potential to increase the anti-MM efficacy of immunotherapy. The aim of the present work was to assess the potential effect of tinostamustine (EDO-S101), a first-in-class alkylating deacetylase inhibitor, in combination with daratumumab, an anti-CD38 monoclonal antibody (mAb), through different preclinical studies. Tinostamustine increases CD38 expression in myeloma cell lines, an effect that occurs in parallel with an increment in CD38 histone H3 acetylation levels. Also, the expression of MICA and MICB, ligands for the NK cell activating receptor NKG2D, augments after tinostamustine treatment in myeloma cell lines and primary myeloma cells. Pretreatment of myeloma cell lines with tinostamustine increased the sensitivity of these cells to daratumumab through its different cytotoxic mechanisms, and the combination of these two drugs showed a higher anti-myeloma effect than individual treatments in ex vivo cultures of myeloma patients' samples. In vivo data confirmed that tinostamustine pretreatment followed by daratumumab administration significantly delayed tumor growth and improved the survival of mice compared to individual treatments. In summary, our results suggest that tinostamustine could be a potential candidate to improve the efficacy of anti-CD38 mAbs.

المؤلفون: Lopez KJ; Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Spence JP; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Li W; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Zhang W; Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Wei B; Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Cross-Najafi AA; Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Butler JR; Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Cooper DKC; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA., Ekser B; Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Li P; Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

المصدر: Cells [Cells] 2023 Nov 07; Vol. 12 (22). Date of Electronic Publication: 2023 Nov 07.

نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

مواضيع طبية MeSH: NK Cell Lectin-Like Receptor Subfamily K*/genetics , NK Cell Lectin-Like Receptor Subfamily K*/metabolism , Endothelial Cells*, Humans ; Animals ; Swine ; Receptors, Natural Killer Cell/metabolism ; Ligands ; Killer Cells, Natural

مستخلص: Natural killer (NK) cells play a vital role in xenotransplantation rejection. One approach to induce NK cell immune tolerance is to prevent the NK cell-mediated direct killing of porcine cells by targeting the interaction of the activating receptor NKG2D and its ligands. However, the identity of porcine ligands for the human NKG2D receptor has remained elusive. Previous studies on porcine UL-16 binding protein 1 (pULBP-1) as a ligand for human NKG2D have yielded contradictory results. The goal of the present study was to clarify the role of pULBP-1 in the immune response and its interaction with human NKG2D receptor. To accomplish this, the CRISPR/Cas9 gene editing tool was employed to disrupt the porcine ULBP-1 gene in a 5-gene knockout porcine endothelial cell line ( GGTA1 , CMAH , β4galNT2 , SLA-I α chain , and β-2 microglobulin , 5GKO). A colony with two allele mutations in pULBP -1 was established as a 6-gene knockout pig cell line (6GKO). We found that pULBP-1-deficient pig cells exhibited a reduced binding capacity to human NKG2D-Fc, a recombinant chimera protein. However, the removal of ULBP-1 from porcine endothelial cells did not significantly impact human NK cell degranulation or cytotoxicity upon stimulation with the pig cells. These findings conclusively demonstrate that pULBP-1 is not a crucial ligand for initiating xenogeneic human NK cell activation.

المؤلفون: Wei L; Department of Immunology, School of Basic Medical, Central South University, Changsha 410083, China., Xiang Z; Department of Immunology, School of Basic Medical, Central South University, Changsha 410083, China., Zou Y; Department of Immunology, School of Basic Medical, Central South University, Changsha 410083, China.

المصدر: International journal of molecular sciences [Int J Mol Sci] 2023 Dec 16; Vol. 24 (24). Date of Electronic Publication: 2023 Dec 16.

نوع المنشور: Journal Article; Review

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

مواضيع طبية MeSH: NK Cell Lectin-Like Receptor Subfamily K*/metabolism , Autoimmune Diseases*/therapy , Autoimmune Diseases*/metabolism, Humans ; CD8-Positive T-Lymphocytes/metabolism ; Ligands ; Killer Cells, Natural ; Immunotherapy

مستخلص: Natural killer (NK) cells and CD8 ⁺ T cells can clear infected and transformed cells and generate tolerance to themselves, which also prevents autoimmune diseases. Natural killer group 2 member D (NKG2D) is an important activating immune receptor that is expressed on NK cells, CD8 ⁺ T cells, γδ T cells, and a very small percentage of CD4 ⁺ T cells. In contrast, the NKG2D ligand (NKG2D-L) is generally not expressed on normal cells but is overexpressed under stress. Thus, the inappropriate expression of NKG2D-L leads to the activation of self-reactive effector cells, which can trigger or exacerbate autoimmunity. In this review, we discuss the role of NKG2D and NKG2D-L in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type I diabetes (T1DM), inflammatory bowel disease (IBD), and celiac disease (CeD). The data suggest that NKG2D and NKG2D-L play a pathogenic role in some autoimmune diseases. Therefore, the development of strategies to block the interaction of NKG2D and NKG2D-L may have therapeutic effects in some autoimmune diseases.

المؤلفون: Kraivong R; Molecular Biology of Dengue and Flaviviruses Research Team, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 12120, Thailand.; Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Punyadee N; Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Liszewski MK; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Atkinson JP; Division of Rheumatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Avirutnan P; Molecular Biology of Dengue and Flaviviruses Research Team, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok 12120, Thailand.; Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

المصدر: Viruses [Viruses] 2021 Jun 24; Vol. 13 (7). Date of Electronic Publication: 2021 Jun 24.

نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE

مواضيع طبية MeSH: Complement Pathway, Mannose-Binding Lectin*, Dengue/*immunology , Dengue/*virology , Dengue Virus/*immunology , Dengue Virus/*pathogenicity, Animals ; Humans ; Immune Evasion ; Mannose-Binding Lectin/blood ; Mannose-Binding Lectin/genetics ; Mannose-Binding Lectin/immunology ; Mannose-Binding Lectin/metabolism ; Polymorphism, Single Nucleotide ; Polysaccharides/immunology ; Polysaccharides/metabolism ; Receptors, Pattern Recognition/blood ; Receptors, Pattern Recognition/genetics ; Receptors, Pattern Recognition/immunology ; Receptors, Pattern Recognition/metabolism ; Severe Dengue/immunology ; Severe Dengue/virology ; Viral Nonstructural Proteins/metabolism ; Virulence

مستخلص: Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system's lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern recognition receptor (PRR) binding efficiency. The important PRR, mannan binding lectin (MBL), mediates DENV neutralization through (1) a complement activation-independent mechanism via direct MBL glycan recognition, thereby inhibiting DENV attachment to host target cells, or (2) a complement activation-dependent mechanism following the attachment of complement opsonins C3b and C4b to virion surfaces. The serum concentrations of lectin PRRs and their polymorphisms influence these LP activities. Conversely, to escape the LP attack and enhance the infectivity, DENV utilizes the secreted form of nonstructural protein 1 (sNS1) to counteract the MBL effects, thereby increasing viral survival and dissemination.

المؤلفون: Pighi C; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Rotili A; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.; PhD Program in 'Immunology, Molecular Medicine and Applied Biotechnologies', Department of Systems Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy., De Luca M; Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Chiurchiù S; Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Calò Carducci FI; Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Rossetti C; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Cifaldi L; Department of Clinical Sciences and Translational Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy., Bei R; Department of Clinical Sciences and Translational Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy., Caforio L; Fetal Medicine and Surgery Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Bernardi S; Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy., Palma P; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.; Department of Systems Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy., Amodio D; Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.; Department of Systems Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy.

المصدر: Viruses [Viruses] 2024 May 14; Vol. 16 (5). Date of Electronic Publication: 2024 May 14.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE

مواضيع طبية MeSH: Killer Cells, Natural*/immunology , Cytomegalovirus Infections*/immunology , Cytomegalovirus Infections*/virology , Cytomegalovirus Infections*/transmission , Pregnancy Complications, Infectious*/virology , Pregnancy Complications, Infectious*/immunology , Infectious Disease Transmission, Vertical* , Cytomegalovirus*/immunology, Humans ; Female ; Pregnancy ; Infant, Newborn ; Adult ; Cohort Studies ; NK Cell Lectin-Like Receptor Subfamily C/metabolism ; Young Adult

مستخلص: Human cytomegalovirus (CMV) is a common herpesvirus causing lifelong latent infection in most people and is a primary cause of congenital infection worldwide. Given the role of NK cells in the materno-fetal barrier, we investigated peripheral blood NK cell behavior in the context of CMV infection acquired during pregnancy. We analyzed the NK phenotype and CD107a surface mobilization on PBMCs from CMV-transmitting and non-transmitting mothers and newborns with or without congenital infection. NK cells from non-transmitting mothers showed the typical phenotype of CMV-adaptive NK cells, characterized by higher levels of NKG2C, CD57, and KIRs, with reduced NKG2A, compared to transmitting ones. A significantly higher percentage of DNAM-1+, PD-1+, and KIR+NKG2A-CD57+PD-1+ CD56dim cells was found in the non-transmitting group. Accordingly, NK cells from congenital-CMV (cCMV)-infected newborns expressed higher levels of NKG2C and CD57, with reduced NKG2A, compared to non-congenital ones. Furthermore, they showed a significant expansion of CD56dim cells co-expressing NKG2C and CD57 or with a memory-like (KIR+NKG2A-CD57+NKG2C+) phenotype, as well as a significant reduction of the CD57-NKG2C- population. Degranulation assays showed a slightly higher CD107a geomean ratio in NK cells of mothers who were non-transmitting compared to those transmitting the virus. Our findings demonstrate that both CMV-transmitting mothers and cCMV newborns show a specific NK profile. These data can guide studies on predicting virus transmission from mothers and congenital infection in infants.

المؤلفون: Faragó A; Astridbio Technologies Ltd., Wimmer Fülöp utca 1, H6728 Szeged, Hungary.; University of Szeged, Albert Szent-Györgyi Medical School, Doctoral School of Multidisciplinary Medical Sciences, Dóm tér 9, H6720 Szeged, Hungary., Zvara Á; Institute of Genetics, Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Core Facility HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary., Tiszlavicz L; Department of Pathology, University of Szeged, Állomás u. 2, H6725 Szeged, Hungary., Hunyadi-Gulyás É; Core Facility HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Laboratory of Proteomics Research, HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary., Darula Z; Core Facility HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Laboratory of Proteomics Research, HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; The Hungarian Centre of Excellence for Molecular Medicine (HCEMM) Single Cell Omics Advanced Core Facility, Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary., Hegedűs Z; Core Facility HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Laboratory of Bioinformatics, HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H7624 Pécs, Hungary., Szabó E; Institute of Genetics, Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Core Facility HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary., Surguta SE; Department of Experimental Pharmacology, The National Tumor Biology Laboratory, National Institute of Oncology, Ráth György u. 7-9, H1122 Budapest, Hungary., Tóvári J; Department of Experimental Pharmacology, The National Tumor Biology Laboratory, National Institute of Oncology, Ráth György u. 7-9, H1122 Budapest, Hungary., Puskás LG; Institute of Genetics, Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Core Facility HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Avidin Ltd., Alsó Kikötő sor 11/D, H6726 Szeged, Hungary.; Avicor Ltd., Alsó Kikötő sor 11/D, H6726 Szeged, Hungary., Szebeni GJ; Astridbio Technologies Ltd., Wimmer Fülöp utca 1, H6728 Szeged, Hungary.; Institute of Genetics, Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Core Facility HUN-REN Biological Research Centre, Temesvári krt. 62, H6726 Szeged, Hungary.; Department of Internal Medicine, Hematology Centre, Faculty of Medicine University of Szeged, H6725 Szeged, Hungary.

المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Apr 04; Vol. 25 (7). Date of Electronic Publication: 2024 Apr 04.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

مواضيع طبية MeSH: Colonic Neoplasms* , Colorectal Neoplasms* , Carcinoma*, Humans ; Animals ; Mice ; Galectin 1 ; Disease Models, Animal ; Immunophenotyping ; Proteomics ; Sialic Acid Binding Ig-like Lectin 1 ; Tomography, X-Ray Computed

مستخلص: A murine colorectal carcinoma (CRC) model was established. CT26 colon carcinoma cells were injected into BALB/c mice's spleen to study the primary tumor and the mechanisms of cell spread of colon cancer to the liver. The CRC was verified by the immunohistochemistry of Pan Cytokeratin and Vimentin expression. Immunophenotyping of leukocytes isolated from CRC-bearing BALB/c mice or healthy controls, such as CD19+ B cells, CD11+ myeloid cells, and CD3+ T cells, was carried out using fluorochrome-labeled lectins. The binding of six lectins to white blood cells, such as galectin-1 (Gal1), siglec-1 (Sig1), Sambucus nigra lectin (SNA), Aleuria aurantia lectin (AAL), Phytolacca americana lectin (PWM), and galectin-3 (Gal3), was assayed. Flow cytometric analysis of the splenocytes revealed the increased binding of SNA, and AAL to CD3 + T cells and CD11b myeloid cells; and increased siglec-1 and AAL binding to CD19 B cells of the tumor-bearing mice. The whole proteomic analysis of the established CRC-bearing liver and spleen versus healthy tissues identified differentially expressed proteins, characteristic of the primary or secondary CRC tissues. KEGG Gene Ontology bioinformatic analysis delineated the established murine CRC characteristic protein interaction networks, biological pathways, and cellular processes involved in CRC. Galectin-1 and S100A4 were identified as upregulated proteins in the primary and secondary CT26 tumor tissues, and these were previously reported to contribute to the poor prognosis of CRC patients. Modelling the development of liver colonization of CRC by the injection of CT26 cells into the spleen may facilitate the understanding of carcinogenesis in human CRC and contribute to the development of novel therapeutic strategies.

المؤلفون: Komuro R; Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan.; Department of RNA Pathobiology and Therapeutics, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan.; Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan., Honda Y; Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan., Yanaizu M; Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan.; Department of RNA Pathobiology and Therapeutics, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan., Nagahama M; Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan., Kino Y; Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan.; Department of RNA Pathobiology and Therapeutics, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose-shi 204-8588, Japan.

المصدر: Cells [Cells] 2023 Feb 13; Vol. 12 (4). Date of Electronic Publication: 2023 Feb 13.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

مواضيع طبية MeSH: Alternative Splicing* , Alzheimer Disease*/metabolism , Sialic Acid Binding Ig-like Lectin 3*/metabolism, Animals ; Humans ; Mice ; Exons ; Protein Isoforms/metabolism ; RNA Splicing

مستخلص: Genetic variations of CD33 have been implicated as a susceptibility factor of Alzheimer's disease (AD). A polymorphism on exon 2 of CD33 , rs12459419, affects the alternative splicing of this exon. The minor allele is associated with a reduced risk of AD and promotes the skipping of exon 2 to produce a shorter CD33 isoform lacking the extracellular ligand-binding domain, leading to decreased suppressive signaling on microglial activity. Therefore, factors that regulate the splicing of exon 2 may alter the disease-associated properties of CD33. Herein, we sought to identify the regulatory proteins of CD33 splicing. Using a panel of RNA-binding proteins and a human CD33 minigene, we found that exon 2 skipping of CD33 was promoted by HNRNPA1. Although the knockdown of HNRNPA1 alone did not reduce exon 2 skipping, simultaneous knockdown of HNRNPA1 together with that of HNRNPA2B1 and HNRNPA3 promoted exon 2 inclusion, suggesting functional redundancy among HNRNPA proteins. Similar redundant regulation by HNRNPA proteins was observed in endogenous CD33 of THP-1 and human microglia-like cells. Although mouse Cd33 showed a unique splicing pattern of exon 2, we confirmed that HNRNPA1 promoted the skipping of this exon. Collectively, our results revealed novel regulatory relationships between CD33 and HNRNPA proteins.