Induction of Tolerogenic Dendritic Cells by NF-kappa B Blockade and Fc gamma Receptor Modulation

Carreno, Leandro J.; Riedel, Claudia A; Kalergis, Alexis M; Cuturi, MC; Anegon, I

Abstract

Autoimmune diseases develop as a result of an unbalanced adaptive immunity that targets self-antigens and causes destruction of healthy host tissues. Maintenance of peripheral immune tolerance to self-antigens is mainly mediated by dendritic cells (DCs), professional antigen-presenting cells that modulate the activation of T cells. Due to their key role as regulators of adaptive immunity, identification of means of enhancing DC tolerogenic capacity and therapeutic potential is a priority goal to reduce autoimmune disease burden in an antigen-specific manner. Our findings suggest novel approaches to enhance DC capacity to induce self-tolerance and reduce the severity of autoimmune disorders. Specifically, we have shown, both in vitro and in vivo, that NF-kappa B blockade on DCs by andrographolide or rosiglitazone can significantly enhance the tolerogenic capacity of DCs. Furthermore, we have observed that expression ratio of the activating Fc gamma RIII or the inhibitory Fc gamma RIIb is determinant for the tolerogenic potential of DCs. In this chapter, we describe the procedures to produce tolerogenic DCs and explain the potential therapeutic use of two NF-kappa B inhibitors for the treatment of autoimmune disease models, such as experimental autoimmune encephalomyelitis (EAE) and systemic lupus erythematosus (SEE) in mice. Therefore, our studies support the notion that Fc gamma Rs and NF-kappa B can be considered as pharmacological targets to increase the capacity of DCs to induce or restore self-tolerance and decrease inflammatory damage to self-tissues.

Más información

Título según WOS: ID WOS:000283520000022 Not found in local WOS DB
Título de la Revista: NEISSERIA MENINGITIDIS
Volumen: 677
Editorial: Humana Press, Inc.
Fecha de publicación: 2011
Página de inicio: 339
Página final: 353
DOI:

10.1007/978-1-60761-869-0_22

Notas: ISI