Paolo Somma

Humanitas University

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Alberto Mantovani

Humanitas University

Tiziana Musso

University of Turin

Giuseppe Tabbia

Azienda Ospedaliera Citta' della Salute e della Scienza di Torino

Silvano Sozzani

Istituto Pasteur

Laura Salogni

University of Brescia

Valentina Salvi

University of Brescia

Sara Scutera

University of Turin

Christian Pasquali

Vifor Pharma (Switzerland)

Xenia Vaira

University of Brescia

Marco Bardessono

Azienda Ospedaliera Citta' della Salute e della Scienza di Torino

Cooperative Institutions

Istituti di Ricovero e Cura a Carattere Scientifico

Humanitas University

IRCCS Humanitas Research Hospital

University of Milan

National Research Council

Fondazione Humanitas per la Ricerca

University of Turin

Institute of Cell Biology and Neurobiology

University of Brescia

Sapienza University of Rome

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Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis

Journal of Leukocyte Biology (2006)

Paolo Somma Giovanni Ristori Luca Battistini Stefania Cannoni Giovanna Borsellino

Abstract Autoreactive CD4+ and CD8+ T cells directed against CNS autoantigens may play a role in the development of multiple sclerosis (MS). Identical twins share the same genetic background but not the TCR repertoire that is shaped by the encounter with self or foreign antigens. To gain insights into the interplay between MS and T cell repertoire, peripheral blood CD4+ and CD8+ T lymphocytes and their CCR7+/CCR7– subsets from five pairs of identical twins (four discordant and one concordant for MS; none of which had taken disease-modifying therapy) were compared by TCR β-chain (TCRB) complementary-determining region 3 (CDR3) spectratyping. CD4+ T cells generally showed a Gaussian distribution, whereas CD8+ T cells exhibited subject-specific, widely skewed TCR spectratypes. There was no correlation between CD8+ T cell oligoclonality and disease. Sequencing of predominant spectratype expansions revealed shared TCRB-CDR3 motifs when comparing inter- and/or intrapair twin members. In many cases, these sequences were homologous to published TCRs, specific for viruses implicated in MS pathogenesis, CNS autoantigens, or copaxone [glatiramer acetate (GA)], implying the occurrence of naturally GA-responding CD8+ T cells. It is notable that these expanded T cell clones with putative pathogenic or regulatory properties were present in the affected as well as in the healthy subject, thus suggesting the existence of a “MS predisposing trait” shared by co-twins discordant for MS.

10.1189/jlb.0906584

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Citations (25)

Extracellular Vesicles from Skeletal Muscle Cells Efficiently Promote Myogenesis in Induced Pluripotent Stem Cells

Cells (2020)

Denisa Baci Maila Chirivì Valentina Pace Fabio Maiullari Marika Milan

The recent advances, offered by cell therapy in the regenerative medicine field, offer a revolutionary potential for the development of innovative cures to restore compromised physiological functions or organs. Adult myogenic precursors, such as myoblasts or satellite cells, possess a marked regenerative capacity, but the exploitation of this potential still encounters significant challenges in clinical application, due to low rate of proliferation in vitro, as well as a reduced self-renewal capacity. In this scenario, induced pluripotent stem cells (iPSCs) can offer not only an inexhaustible source of cells for regenerative therapeutic approaches, but also a valuable alternative for in vitro modeling of patient-specific diseases. In this study we established a reliable protocol to induce the myogenic differentiation of iPSCs, generated from pericytes and fibroblasts, exploiting skeletal muscle-derived extracellular vesicles (EVs), in combination with chemically defined factors. This genetic integration-free approach generates functional skeletal myotubes maintaining the engraftment ability in vivo. Our results demonstrate evidence that EVs can act as biological “shuttles” to deliver specific bioactive molecules for a successful transgene-free differentiation offering new opportunities for disease modeling and regenerative approaches.

Extracellular Vesicles

10.3390/cells9061527

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Citations (19)

Expression and function of IL-1R8 (TIR8/SIGIRR), a regulatory member of the IL-1 receptor family in platelets

Cardiovascular Research (2016)

Achille Anselmo Federica Riva Stefania Gentile Cristiana Soldani Marialuisa Barbagallo

Aims Platelets express functional interleukin-1 receptor-1 (IL-1R1) as well as a repertoire of toll-like receptors (TLRs) involved in platelet activation, platelet–leucocyte reciprocal activation, and immunopathology. IL-1R8, also known as single Ig IL-1-related receptor (SIGIRR) or TIR8, is a member of the IL-1R family that negatively regulates responses to IL-1R family members and TLRs. In the present study, we addressed the expression of IL-1R8 in platelets and megakaryocytes and its role in the control of platelet activation during inflammatory conditions and thromboembolism. Methods and results Here, we show by flow cytometry analysis, western blot, confocal microscopy, and quantitative real-time polymerase chain reaction that IL-1R8 is expressed on human and mouse platelets at high levels and on megakaryocytes. IL-1R8-deficient mice show normal levels of circulating platelets. Homotypic and heterotypic (platelet–neutrophil) aggregation triggered by Adenosine DiPhosphate (ADP) and IL-1 or lipopolysaccharide (LPS) was increased in IL-1R8-deficient platelets. IL-1R8-deficient mice showed increased soluble P-selectin levels and increased platelet–neutrophil aggregates after systemic LPS administration. Commensal flora depletion and IL-1R1 deficiency abated platelet hyperactivity and the increased platelet/neutrophil aggregation observed in Il1r8−/− mice in vitro and in vivo, suggesting a key role of IL-1R8 in regulating platelet TLR and IL-1R1 function. In a mouse model of platelet-dependent pulmonary thromboembolism induced by ADP administration, IL-1R8-deficient mice showed an increased frequency of blood vessel complete obstruction. Conclusion These results show that platelets, which have a large repertoire of TLRs and IL-1 receptors, express high levels of IL-1R8, which plays a non-redundant function as a regulator of thrombocyte activity in vitro and in vivo.

10.1093/cvr/cvw162

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Selective Activation of Human Dendritic Cells by OM-85 through a NF-kB and MAPK Dependent Pathway

PLoS ONE (2013)

Carmen Parola Laura Salogni Xenia Vaira Sara Scutera Paolo Somma

OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), a product made of the water soluble fractions of 21 inactivated bacterial strain patterns responsible for respiratory tract infections, is used for the prevention of recurrent upper respiratory tract infections and acute exacerbations in chronic obstructive pulmonary disease patients. OM-85 is able to potentiate both innate and adaptive immune responses. However, the molecular mechanisms responsible for OM-85 activation are still largely unknown. Purpose of this study was to investigate the impact of OM-85 stimulation on human dendritic cell functions. We show that OM-85 selectively induced NF-kB and MAPK activation in human DC with no detectable action on the interferon regulatory factor (IRF) pathway. As a consequence, chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) and B-cell activating cytokines (i.e. IL-6, BAFF and IL-10) were strongly upregulated. OM-85 also synergized with the action of classical pro-inflammatory stimuli used at suboptimal concentrations. Peripheral blood mononuclear cells from patients with COPD, a pathological condition often associated with altered PRR expression pattern, fully retained the capability to respond to OM-85. These results provide new insights on the molecular mechanisms of OM-85 activation of the immune response and strengthen the rational for its use in clinical settings.

CCL20

Interleukin 8

10.1371/journal.pone.0082867

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Citations (55)

Flow Cytometry Detection of Chemokine Receptors for the Identification of Murine Monocyte and Neutrophil Subsets

Methods in enzymology on CD-ROM/Methods in enzymology (2015)

Ornella Bonavita Matteo Massara Achille Anselmo Paolo Somma Hilke Brühl

Monocyte

CCR2

CCR1

CCL13