Obiettivo Anti-nuclear antibodies (ANAs) are the most common types of autoantibodies in SLE. Elevated levels of ANAs belonging to the IgD class have long been observed in SLE patients, reflecting dysregulation of the IgD compartment, but the significance of this dysregulation in SLE pathogenesis is completely unknown. IgD in healthy individuals reacts more frequently with nuclear antigens than IgG, the antibody class well-recognized in SLE pathogenesis.The unique properties of IgD, such as the positively charged amino acids in its long hinge region and its high degrees of somatic hypermutation, mayenable IgD to bind many SLE-associated antigens, such as negatively charged double-stranded DNA. These features highlight the strong pathogenicpotential of IgD in SLE. We recently discovered that a discrete subset of B cells undergoes a non-canonical form of IgM-to-IgD class switching upon exposure to a specific cocktail of cytokines, including interleukin-21 (IL-21). We also found that IgD binds to myeloid cells such as basophils, mast cells, monocytes and neutrophils, and induces potent inflammatory responses from these cells, including IL-1 and IL-18 production. The present project aims at elucidating the mechanism of dysregulated IgD production in SLE and the function of IgD in SLE-associated inflammation. We hypothesize that elevated IgD production in SLE originates from a pathological imbalance between IgD-inducing and IgD-restraining signals in B cells, including autoreactive B cells.We contend that such imbalance leads to an increased production of IgD antibodies highly reactive to self-antigens, including autologous double-stranded DNA. We argue that this process enhances inflammation by activating interleukin-1 and interleukin-18-processing signaling platforms in myeloid cells. Campo scientifico natural sciencesbiological sciencesgeneticsDNAnatural scienceschemical sciencesorganic chemistryamines Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Invito a presentare proposte FP7-PEOPLE-2010-RG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IRG - International Re-integration Grants (IRG) Coordinatore FUNDACIO INSTITUT HOSPITAL DEL MAR D INVESTIGACIONS MEDIQUES Contributo UE € 100 000,00 Indirizzo Doctor Aiguader 88 08003 Barcelona Spagna Mostra sulla mappa Regione Este Cataluña Barcelona Tipo di attività Research Organisations Contatto amministrativo Miguel López-Botet (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
