Document Detail


PD-1 on immature and PD-1 ligands on migratory human Langerhans cells regulate antigen-presenting cell activity.
MedLine Citation:
PMID:  20445553     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Langerhans cells (LCs) are known as "sentinels" of the immune system that function as professional antigen-presenting cells (APCs) after migration to draining lymph node. LCs are proposed to have a role in tolerance and the resolution of cutaneous immune responses. The Programmed Death-1 (PD-1) receptor and its ligands, PD-L1 and PD-L2, are a co-inhibitory pathway that contributes to the negative regulation of T-lymphocyte activation and peripheral tolerance. Surprisingly, we found PD-1 to be expressed on immature LCs (iLCs) in situ. PD-1 engagement on iLCs reduced IL-6 and macrophage inflammatory protein (MIP)-1alpha cytokine production in response to TLR2 signals but had no effect on LC maturation. PD-L1 and PD-L2 were expressed at very low levels on iLCs. Maturation of LCs upon migration from epidermis led to loss of PD-l expression and gain of high expression of PD-L1 and PD-L2 as well as co-stimulatory molecules. Blockade of PD-L1 and/or PD-L2 on migratory LCs (mLCs) and DDCs enhanced T-cell activation, as has been reported for other APCs. Thus the PD-1 pathway is active in iLCs and inhibits iLC activities, but expression of receptor and ligands reverses upon maturation and PD-L1 and PD-L2 on mLC function to inhibit T-cell responses.
Authors:
Victor Peña-Cruz; Sean M McDonough; Felipe Diaz-Griffero; Christopher P Crum; Ruben D Carrasco; Gordon J Freeman
Related Documents :
15654963 - Tgfbeta inhibits cd1d expression on dendritic cells.
17130243 - Murine cxcl14 is dispensable for dendritic cell function and localization within periph...
16374213 - Immune reconstitution inflammatory syndrome in hiv.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-05-06
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  130     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-09-16     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2222-30     Citation Subset:  IM    
Affiliation:
Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antigen Presentation / immunology*
Antigens, CD / metabolism*
Antigens, CD80 / metabolism
Antigens, CD86 / metabolism
Apoptosis Regulatory Proteins / metabolism*
Cell Communication / immunology
Cell Differentiation / immunology
Cell Movement / immunology*
Cytokines / metabolism
Humans
Immunoglobulins / metabolism
Immunophenotyping
Intercellular Signaling Peptides and Proteins / metabolism*
Jurkat Cells
Langerhans Cells / immunology,  metabolism*
Ligands
Lymphocyte Activation / immunology
Membrane Glycoproteins / metabolism
Signal Transduction / immunology
Toll-Like Receptor 2 / agonists,  metabolism
Up-Regulation / immunology
Grant Support
ID/Acronym/Agency:
A1056299//PHS HHS; A108080192//PHS HHS; BAA-05-11//PHS HHS; HHSN266200500030C//PHS HHS; P01 AI056299-06A17716/AI/NIAID NIH HHS; P01 AI056299-077716/AI/NIAID NIH HHS; P01 AI080192-019001/AI/NIAID NIH HHS; P01 AI080192-029001/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD80; 0/Antigens, CD86; 0/Apoptosis Regulatory Proteins; 0/B7-DC antigen; 0/CD274 protein, human; 0/CD83 antigen; 0/CD86 protein, human; 0/Cytokines; 0/Immunoglobulins; 0/Intercellular Signaling Peptides and Proteins; 0/Ligands; 0/Membrane Glycoproteins; 0/TLR2 protein, human; 0/Toll-Like Receptor 2; 146588-21-8/PDCD1 protein, human
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Psoriasis and Systemic Inflammatory Diseases: Potential Mechanistic Links between Skin Disease and C...
Next Document:  IL-17A Has an Important Role in the Acute Attacks of Beh??et's Disease.