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Induction of Tolerogenic Dendritic Cells by NF-κB Blockade and Fcγ Receptor Modulation

  • Leandro J. Carreño
  • Claudia A. Riedel
  • Alexis M. Kalergis
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 677)

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-κB 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 FcγRIII or the inhibitory FcγRIIb 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-κB inhibitors for the treatment of autoimmune disease models, such as experimental autoimmune encephalomyelitis (EAE) and systemic lupus erythematosus (SLE) in mice. Therefore, our studies support the notion that FcγRs and NF-κB 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.

Key words

Dendritic cells NF-κB Andrographolide Rosiglitazone Fcγ receptors EAE SLE 

Notes

Acknowledgments

Authors would like to thank all the trainees who contributed to the articles from our group cited in this publication. This work was supported by Grants FONDECYT 1070352 and 1085281 and Millennium Nucleus on Immunology and Immunotherapy (P07/088-F)

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Copyright information

© Humana Press 2010

Authors and Affiliations

  • Leandro J. Carreño
    • 1
  • Claudia A. Riedel
    • 2
  • Alexis M. Kalergis
    • 3
  1. 1.Millenium Nucleus of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias BiológicasPontificia Universidad Catolica de ChileSantiagoChile
  2. 2.Millenium Nucleus of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Laboratorio de Biología Celular y Farmacología, Departamento de Ciencias Biológicas, Facultad de Ciencias BiológicasPontificia Universidad Catolica de ChileSantiagoChile
  3. 3.Millenium Nucleus of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Departamento de Reumatología, Facultad de MedicinaPontificia Universidad Catolica de ChileSantiagoChile

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