Document Detail


Specialized role of migratory dendritic cells in peripheral tolerance induction.
MedLine Citation:
PMID:  23298832     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Harnessing DCs for immunotherapies in vivo requires the elucidation of the physiological role of distinct DC populations. Migratory DCs traffic from peripheral tissues to draining lymph nodes charged with tissue self antigens. We hypothesized that these DC populations have a specialized role in the maintenance of peripheral tolerance, specifically, to generate suppressive Foxp3+ Tregs. To examine the differential capacity of migratory DCs versus blood-derived lymphoid-resident DCs for Treg generation in vivo, we targeted a self antigen, myelin oligodendrocyte glycoprotein, using antibodies against cell surface receptors differentially expressed in these DC populations. Using this approach together with mouse models that lack specific DC populations, we found that migratory DCs have a superior ability to generate Tregs in vivo, which in turn drastically improve the outcome of experimental autoimmune encephalomyelitis. These results provide a rationale for the development of novel therapies targeting migratory DCs for the treatment of autoimmune diseases.
Authors:
Juliana Idoyaga; Christopher Fiorese; Lori Zbytnuik; Ashira Lubkin; Jennifer Miller; Bernard Malissen; Daniel Mucida; Miriam Merad; Ralph M Steinman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-09
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  844-54     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / immunology
Antigens, Surface / immunology
Autoantigens
Cell Movement / immunology
Dendritic Cells / classification,  immunology*,  physiology
Encephalomyelitis, Autoimmune, Experimental / immunology
Forkhead Transcription Factors / metabolism
Langerhans Cells / immunology,  physiology
Lectins, C-Type / antagonists & inhibitors,  deficiency,  genetics,  immunology
Mannose-Binding Lectins / antagonists & inhibitors,  immunology
Mice
Mice, Knockout
Myelin-Oligodendrocyte Glycoprotein / immunology
Peripheral Tolerance / immunology*,  physiology
Receptors, Cell Surface / antagonists & inhibitors,  immunology
Receptors, Immunologic / deficiency,  genetics,  immunology
T-Lymphocytes, Regulatory / immunology
Grant Support
ID/Acronym/Agency:
1K99AR062595/AR/NIAMS NIH HHS; AI13013/AI/NIAID NIH HHS; K99 AR062595/AR/NIAMS NIH HHS; R01 AI013013/AI/NIAID NIH HHS; U01 AI095611/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Surface; 0/Autoantigens; 0/Cd207 protein, mouse; 0/DEC-205 receptor; 0/Dcir protein, mouse; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Lectins, C-Type; 0/Mannose-Binding Lectins; 0/Mog protein, mouse; 0/Myelin-Oligodendrocyte Glycoprotein; 0/Receptors, Cell Surface; 0/Receptors, Immunologic; 0/Treml4 protein, mouse
Comments/Corrections

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