Search results for "Regulatory"
showing 10 items of 740 documents
CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.
2008
T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcεRI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells and MCs, respectively. When activated in the presence of Treg cells, MCs showed increased cyclic adenosine monophosphate (cAMP) concentrations and reduced Ca2+ influx, independently of phospholipase C (PLC)-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effec…
Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G
2010
LT-R192G, a mutant of the thermolabile enterotoxin of E. coli, is a potent adjuvant of immunization. Immune responses are generally analyzed at the end of protocols including at least 2 administrations, but rarely after a prime. To investigate this point, we compared B and T cell responses in mice after one and two intrarectal immunizations with 2/6 rotavirus-like particles (2/6-VLP) and LT-R192G. After a boost, we found, an unexpected lower B cell expansion measured by flow cytometry, despite a secondary antibody response. We then analyzed CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) and CD4(+)CD25(+)Foxp3(-) helper T cells after in vitro (re)stimulation of mesenteric lymph node cells …
Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo.
2006
Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -independent signaling pathways, we wondered if the simultaneous activation of these signaling cascades would synergize with respect to DC activation and induce superior cytotoxic T-lymphocyte (CTL) activity in vivo. We observed that indeed the combined activation of MyD88-dependent and -independent signaling induced by TLR7 and TLR3 ligands provoked a more rapid and more sustained bone marrow–der…
Infectious Tolerance
2002
Regulatory CD4(+)CD25(+) T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact-mediated suppression of conventional CD4(+) T cells by human CD25(+) Treg cells is fixation resistant, independent from membrane-bound TGF-beta but requires activation and protein synthesis of CD25(+) Treg cells. Coactivation of CD25(+) Treg cells with Treg cell-depleted CD4(+) T cells results in anergized CD4(+) T cells that in turn inhibit the activation of conventional, freshly isolated CD4(+) T helper (Th) cells. This infectious suppressive activity, transferred from CD25(+) Treg cells via cell contact, is cell contact-independent and partially medi…
Binding properties and stability of the Ras-association domain of Rap1-GTP interacting adapter molecule (RIAM).
2012
The Rap1-GTP interacting adapter protein (RIAM) is an important protein in Rap1-mediated integrin activation. By binding to both Rap1 GTPase and talin, RIAM recruits talin to the cell membrane, thus facilitating talin-dependent integrin activation. In this article, we studied the role of the RIAM Ras-association (RA) and pleckstrin-homology (PH) domains in the interaction with Rap1. We found that the RA domain was sufficient for GTP-dependent interaction with Rap1B, and the addition of the PH domain did not change the binding affinity. We also detected GTP-independent interaction of Rap1B with the N-terminus of RIAM. In addition, we found that the PH domain stabilized the RA domain both in …
The histone deacetylase Rpd3 regulates the heterochromatin structure of Drosophila telomeres
2011
Telomeres are specialized structures at the end of eukaryotic chromosomes that are required to preserve genome integrity, chromosome stability and nuclear architecture. Telomere maintenance and function are established epigenetically in several eukaryotes. However, the exact chromatin enzymatic modifications regulating telomere homeostasis are poorly understood. In Drosophila melanogaster, telomere length and stability are maintained through the retrotransposition of specialized telomeric sequences and by the specific loading of protecting capping proteins, respectively. Here, we show that the loss of the essential and evolutionarily conserved histone deacetylase Rpd3, the homolog of mammal…
Il ruolo del white paper sulle offerte al pubblico di cripto-attività alla luce della proposta MiCA
2022
La proposta MiCA, nel regolare il white paper sulle offerte di crypto-assets, sembra tenere in considerazione i benefici e i limiti dei sistemi di voluntary e di mandatory disclosure, non optando integralmente né per il primo, né per il secondo. In quest’ottica, se può condividersi l’approccio regolamentare diretto a graduare, a seconda della tipologia di token offerto, sia il contenuto che l’assoggettamento del documento a mera notifica o ad approvazione ex ante da parte dell’Autorità competente, dubbi sorgono in ordine all’indistinta allocazione dell’onere della prova in capo all’oblato, nei casi di violazione della disciplina del relativo white paper.
CONCESSIONI DEMANIALI MARITTIME E DIRITTO EUROUNITARIO: LA FINE DEL TEMPO DELLE MORE
2023
Il contributo analizza il frammentario quadro normativo delle concessioni demaniali marittime, lacuali e fluviali con finalità turistico-ricreativa alla luce degli orientamenti della giurisprudenza domestica, con le significative pronunce del Consiglio di Stato e di quella della Corte di Giustizia dell’Unione europea, in particolare della recentissima sentenza 20 aprile 2023 (C-348/22).
Tutela e sicurezza del lavoro tra centro e periferia: la sicurezza sui luoghi di lavoro
2013
Il saggio prende in esame la complessa questione del riparto di competenze tra Stato e Regioni alla luce del Titolo V della Costituzione in materia di salute e sicurezza sui luoghi di lavoro. Il riparto di competenze tra centro e periferia è stato oggetto di una limitata analisi da parte della dottrina e della giurisprudenza, che si sono concentrate in particolare sulla disciplina del mercato del lavoro. L’Autore descrive un sistema multilivello, caratterizzato dalla compresenza di fonti nazionali e regionali, della contrattazione collettiva, nonché di codici di condotta. Sulla scorta di una ricostruzione del quadro normativo e dei percorsi della giurisprudenza, il saggio propone una lettur…
Let-7d miRNA Shows Both Antioncogenic and Oncogenic Functions in Osteosarcoma-Derived 3AB-OS Cancer Stem Cells
2015
Osteosarcoma (OS), an aggressive highly invasive and metastatic bone-malignancy, shows therapy resistance and recurrence, two features that likely depend on cancer stem cells (CSCs), which hold both self-renewing and malignant potential. So, effective anticancer therapies against OS should specifically target and destroy CSCs. We previously found that the let-7d microRNA was downregulated in the 3AB-OS-CSCs, derived from the human OS-MG63 cells. Here, we aimed to assess whether let-7d modulation affected tumorigenic and stemness properties of these OS-CSCs. We found that let-7d-overexpression reduced cell proliferation by decreasing CCND2 and E2F2 cell-cycle-activators and increasing p21 an…