Document Detail


Induction of tolerogenic dendritic cells by NF-κB blockade and Fcγ receptor modulation.
MedLine Citation:
PMID:  20941620     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Leandro J Carreño; Claudia A Riedel; Alexis M Kalergis
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Methods in molecular biology (Clifton, N.J.)     Volume:  677     ISSN:  1940-6029     ISO Abbreviation:  Methods Mol. Biol.     Publication Date:  2011  
Date Detail:
Created Date:  2010-10-13     Completed Date:  2011-02-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9214969     Medline TA:  Methods Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  339-53     Citation Subset:  IM    
Affiliation:
Millenium Nucleus of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Catolica de Chile, Santiago, Chile.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen-Presenting Cells / immunology*,  physiology
Autoantigens / immunology
Autoimmune Diseases / immunology*
Autoimmunity / immunology
Dendritic Cells / physiology*
Encephalomyelitis, Autoimmune, Experimental / immunology
Immune Tolerance / immunology*
Lupus Erythematosus, Systemic / immunology
Mice
NF-kappa B / antagonists & inhibitors*
Organic Chemicals / metabolism
Receptors, IgG / genetics,  metabolism*
Self Tolerance / immunology
Transcription Factor RelA / metabolism
Chemical
Reg. No./Substance:
0/Autoantigens; 0/NF-kappa B; 0/Organic Chemicals; 0/Receptors, IgG; 0/Tolerogen; 0/Transcription Factor RelA

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