Papers by Elisabetta Volpe
<strong>Introduction</strong> T helper (Th) 17 cells are a subtype of CD4 T lymphocyt... more <strong>Introduction</strong> T helper (Th) 17 cells are a subtype of CD4 T lymphocytes characterized by the expression of retinoic acid-receptor (RAR)-related orphan receptor (ROR)γt transcription factor, encoded by gene <em>Rorc</em>. These cells are implicated in the pathology of autoimmune inflammatory disorders as well as in the clearance of extracellular infections. The main function of Th17 cells is the production of cytokine called interleukin (IL)-17A. <strong>Methods</strong> We described the lineage defining transcription factor RORγt and other factors that regulate transcription of <em>Il17a, Rorc </em>and Th17-related genes, such as Il17f, Il21, Il23r, which may positively or negatively influence their expression. <strong>Results</strong> We discussed the potential new therapeutic approaches for Th17-related diseases targeting these transcription factors. The wide knowledge of transcriptional regulators of Th17 cells is crucial for the better understanding of the pathogenic role of these cells and for development of therapeutic strategies aimed at fighting Th17-related diseases.
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Methods in Molecular Biology, 2021
T helper (Th) cells are involved in various physiopathological systems, including response to inf... more T helper (Th) cells are involved in various physiopathological systems, including response to infections, vaccination, cancer, and autoimmunity. The isolation of viable human Th cells is a procedure that allows a broad study of both phenotypical and functional features of each Th subset, and thus, it is necessary to study these cells in different contexts. In particular, the purification of human memory Th cells from peripheral blood is preparatory for further complex experiments on these cells, such as global transcriptional analysis, coculture assays, silencing experiments, and drug assays.Here, we describe the method for the identification and isolation of pure memory human Th1, Th2, Th17, Th1/17, and T regulatory cells, derived from peripheral blood mononuclear cells. Moreover, we show the purity of each purified Th subset, verified by the analysis of specific transcription factors.
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Life Science Alliance, 2020
Sam68 ensures the establishment of neuromuscular junctions (NMJs) and motor unit integrity by orc... more Sam68 ensures the establishment of neuromuscular junctions (NMJs) and motor unit integrity by orchestrating a neuronal splicing program. RNA-binding proteins orchestrate the composite life of RNA molecules and impact most physiological processes, thus underlying complex phenotypes. The RNA-binding protein Sam68 regulates differentiation processes by modulating splicing, polyadenylation, and stability of select transcripts. Herein, we found that Sam68−/− mice display altered regulation of alternative splicing in the spinal cord of key target genes involved in synaptic functions. Analysis of the motor units revealed that Sam68 ablation impairs the establishment of neuromuscular junctions and causes progressive loss of motor neurons in the spinal cord. Importantly, alterations of neuromuscular junction morphology and properties in Sam68−/− mice correlate with defects in muscle and motor unit integrity. Sam68−/− muscles display defects in postnatal development, with manifest signs of at...
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Das TSLP wurde vormals als das proallergische Hauptzytokin bei Atopischer Dermatitis (AD) beschri... more Das TSLP wurde vormals als das proallergische Hauptzytokin bei Atopischer Dermatitis (AD) beschrieben. In dieser Studie zeigt sich, dass TSLP ein Teil der humanen Psoriasis-Pathophysiologie ist. TSLP wird in den Keratinozyten der Psoriasis-Patienten gebildet. Es aktiviert die pathogene IL-23-Produktion durch Dendritische Zellen (DCs). Folglich könnte TSLP ein neues Ziel für eine aussichtsreiche Therapieoption bei Psoriasis sein.
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OBJECTIVE Air pollution has been recently identified as a risk factor for multiple sclerosis. Aim... more OBJECTIVE Air pollution has been recently identified as a risk factor for multiple sclerosis. Aim of this study was to investigate the immunological mechanism underlying the clinical association between air pollution, namely exposure to particulate matter 10 (PM10), and inflammatory activity of multiple sclerosis (MS) METHODS Daily recording of PM10 was obtained by monitors depending on the residence of subjects. Expression of molecules involved in activation, adhesion and migration of T lymphocytes were tested by flow-cytometry in 57 MS patients. We next assessed in vitro the effect of PM10 on expression of C-C chemokine receptors 6 (CCR6) by peripheral blood mononuclear cells (PBMCs), on cytokine production by monocyte-derived dendritic cells (mdDC) and on T cell polarization in PBMC/mdDC mixed cultures. RESULTS We identified a significant correlation between mean PM10 levels and expression of CCR6 CD4 + T circulating cells in MS patients. This was paralleled by the observation in...
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Journal of Biological Chemistry, 2013
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Methods in molecular biology, 2021
T helper (Th) cells are involved in various physiopathological systems, including response to inf... more T helper (Th) cells are involved in various physiopathological systems, including response to infections, vaccination, cancer, and autoimmunity. The isolation of viable human Th cells is a procedure that allows a broad study of both phenotypical and functional features of each Th subset, and thus, it is necessary to study these cells in different contexts. In particular, the purification of human memory Th cells from peripheral blood is preparatory for further complex experiments on these cells, such as global transcriptional analysis, coculture assays, silencing experiments, and drug assays.Here, we describe the method for the identification and isolation of pure memory human Th1, Th2, Th17, Th1/17, and T regulatory cells, derived from peripheral blood mononuclear cells. Moreover, we show the purity of each purified Th subset, verified by the analysis of specific transcription factors.
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Frontiers in Immunology, 2021
Primary-progressive (PP) and secondary-progressive (SP) multiple sclerosis (MS) are characterized... more Primary-progressive (PP) and secondary-progressive (SP) multiple sclerosis (MS) are characterized by neurological deficits caused by a permanent neuronal damage, clinically quantified by the expanded disability status scale (EDSS). Neuronal tissue damage is also mediated by immune infiltrates producing soluble factors, such as cytokines and chemokines, which are released in the cerebrospinal fluid (CSF). The mechanisms regulating the production of a soluble factor are not completely defined. Using multiplex bead-based assays, we simultaneously measured 27 immune soluble factors in the CSF collected from 38 patients, 26 with PP-MS and 12 with SP-MS. Then, we performed a correlation matrix of all soluble factors expressed in the CSF. The CSF from patients with PP-MS and SP-MS had similar levels of cytokines and chemokines; however, the stratification of patients according to active or inactive magnetic resonance imaging (MRI) unveils some differences. Correlative studies between solub...
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Frontiers in Immunology
Saccharomyces cerevisiae is a commensal yeast colonizer of mucosal surfaces and an emerging oppor... more Saccharomyces cerevisiae is a commensal yeast colonizer of mucosal surfaces and an emerging opportunistic pathogen in the mucosa and bloodstream. The role of S. cerevisiae has been largely characterized in peripheral blood mononuclear cells and monocyte-derived dendritic cells, where yeast cells induce the production of inflammatory cytokines through the interaction with mannose receptors, chitin receptors, DC SIGN, and dectin1. However, the response of blood-circulating dendritic cells (DCs) to S. cerevisiae has never been investigated. Among blood DCs, conventional DCs (cDCs) are producers of inflammatory cytokines, while plasmacytoid DCs (pDCs) are a specialized population producing a large amount of interferon (IFN)-α, which is involved in the antiviral immune response. Here we report that both human DC subsets are able to sense S. cerevisiae. In particular, cDCs produce interleukin (IL)-6, express activation markers, and promotes T helper 17 cell polarization in response to yea...
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iScience
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Journal of Neuroinflammation
Background Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating... more Background Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating disease of the central nervous system (CNS). Several cytokines are thought to be involved in the regulation of MS pathogenesis. We recently identified interleukin (IL)-9 as a cytokine reducing inflammation and protecting from neurodegeneration in relapsing–remitting MS patients. However, the expression of IL-9 in CNS, and the mechanisms underlying the effect of IL-9 on CNS infiltrating immune cells have never been investigated. Methods To address this question, we first analyzed the expression levels of IL-9 in post-mortem cerebrospinal fluid of MS patients and the in situ expression of IL-9 in post-mortem MS brain samples by immunohistochemistry. A complementary investigation focused on identifying which immune cells express IL-9 receptor (IL-9R) by flow cytometry, western blot, and immunohistochemistry. Finally, we explored the effect of IL-9 on IL-9-responsive cells, analyzing the in...
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Cells
Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by the progressive l... more Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by the progressive loss of axonal myelin in several areas of the central nervous system (CNS) that is responsible for clinical symptoms such as muscle spasms, optic neuritis, and paralysis. The progress made in more than one decade of research in animal models of MS for clarifying the pathophysiology of MS disease validated the concept that MS is an autoimmune inflammatory disorder caused by the recruitment in the CNS of self-reactive lymphocytes, mainly CD4+ T cells. Indeed, high levels of T helper (Th) cells and related cytokines and chemokines have been found in CNS lesions and in cerebrospinal fluid (CSF) of MS patients, thus contributing to the breakdown of the blood–brain barrier (BBB), the activation of resident astrocytes and microglia, and finally the outcome of neuroinflammation. To date, several types of Th cells have been discovered and designated according to the secreted lineage-defining cytok...
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Frontiers in Immunology
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International Journal of Molecular Sciences
Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central n... more Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. The cause of multiple sclerosis is unknown but there are several evidences that associate the genetic basis of the disease with environmental causes. An important association between viral infection and development of MS is clearly demonstrated. Viruses have a strong impact on innate immune cells. In particular, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), are able to respond to viruses and to activate the adaptive immune response. Methods: In this study we mimic viral infection using synthetic single-strand RNA, Resiquimod, and we compared the response of both DC subsets derived from healthy donors and MS patients by characterizing the expression of costimulatory molecules on the DC surface. Results: We found that pDCs from MS patients express higher levels of OX40-L, HLA-DR, and CD86 than healthy donors. Moreover, we found that blood cells from...
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Cells
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). T ... more Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). T helper (Th) 17 lymphocytes play a role in the pathogenesis of MS. Indeed, Th17 cells are abundant in the cerebrospinal fluid and peripheral blood of MS patients and promote pathogenesis in the mouse model of MS. To gain insight into the function of Th17 cells in MS, we tested whether Th17 cells polarized from naïve CD4 T cells of healthy donors and MS patients display different features. To this end, we analysed several parameters that typify the Th17 profile during the differentiation process of naïve CD4 T cells obtained from relapsing-remitting (RR)-MS patients (n = 31) and healthy donors (HD) (n = 28). Analysis of an array of cytokines produced by Th17 cells revealed that expression of interleukin (IL)-21, tumour necrosis factor (TNF)-β, IL-2 and IL-1R1 is significantly increased in Th17 cells derived from MS patients compared to healthy donor-derived cells. Interestingly, IL-1R1 exp...
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Developmental Cell
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International Journal of Molecular Sciences
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Cell death and differentiation, Jan 26, 2018
Polarization of naive T cells into interferon (IFN)-γ-producing T helper 1 (Th1) cells is an esse... more Polarization of naive T cells into interferon (IFN)-γ-producing T helper 1 (Th1) cells is an essential event in the inflammatory response to pathogens. Herein, we identify the RNA binding protein Sam68 as a specific modulator of Th1 differentiation. Sam68-knockout (ko) naive T cells are strongly defective in IL-12-mediated Th1 polarization and express low levels of T-bet and Eomes. Consequently, Sam68-ko Th1 cells are significantly impaired in IFN-γ production. Moreover, we found that Sam68 is required for the induction of an inflammatory Th1 response during Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection, thus limiting bacterial dissemination in the lungs. Mechanistically, Sam68 directly binds to the microRNA miR-29, a negative regulator of Th1 response, and inhibits its expression during BCG infection. These findings uncover a novel post-transcriptional mechanism required for the Th1-mediated defense against intracellular pathogens and identify a new function for Sam6...
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Clinical Cancer Research
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Papers by Elisabetta Volpe