Mannose receptor induces T-cell tolerance via inhibition of CD45 and up-regulation of CTLA-4.
Proc Natl Acad Sci U S A
; 113(38): 10649-54, 2016 09 20.
Article
in En
| MEDLINE
| ID: mdl-27601670
ABSTRACT
The mannose receptor (MR) is an endocytic receptor involved in serum homeostasis and antigen presentation. Here, we identify the MR as a direct regulator of CD8(+) T-cell activity. We demonstrate that MR expression on dendritic cells (DCs) impaired T-cell cytotoxicity in vitro and in vivo. This regulatory effect of the MR was mediated by a direct interaction with CD45 on the T cell, inhibiting its phosphatase activity, which resulted in up-regulation of cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) and the induction of T-cell tolerance. Inhibition of CD45 prevented expression of B-cell lymphoma 6 (Bcl-6), a transcriptional inhibitor that directly bound the CTLA-4 promoter and regulated its activity. These data demonstrate that endocytic receptors expressed on DCs contribute to the regulation of T-cell functionality.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocyte Activation
/
Leukocyte Common Antigens
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Receptors, Cell Surface
/
Lectins, C-Type
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Mannose-Binding Lectins
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CTLA-4 Antigen
Limits:
Animals
/
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2016
Document type:
Article