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The C-type lectin-like receptor CLEC-1, expressed by myeloid cells and endothelial cells, is up-regulated by immunoregulatory mediators and moderates T cell activation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2009 Sep 01; Vol. 183 (5), pp. 3099-108. Date of Electronic Publication: 2009 Aug 10. - Publication Year :
- 2009
-
Abstract
- C-type lectin receptors have recently been described as playing crucial roles in immunity and homeostasis since these proteins are able to recognize pathogens as well as self-Ags. We identified the C-type lectin-like receptor-1, CLEC-1, as being overexpressed in a model of rat allograft tolerance. We previously described in this model the expression of numerous cytoprotective molecules by graft endothelial cells and their interplay with regulatory CD4(+)CD25(+) T cells. In this study, we demonstrate that CLEC-1 is expressed by myeloid cells and specifically by endothelial cells in tolerated allografts and that CLEC-1 expression can be induced in endothelial cells by alloantigen-specific regulatory CD4(+)CD25(+) T cells. Analysis of CLEC-1 expression in naive rats demonstrates that CLEC-1 is highly expressed by myeloid cells and at a lower level by endothelial cells, and that its expression is down-regulated by inflammatory stimuli but increased by the immunoregulators IL-10 or TGFbeta. Interestingly, we demonstrate in vitro that inhibition of CLEC-1 expression in rat dendritic cells increases the subsequent differentiation of allogeneic Th17 T cells and decreases the regulatory Foxp3(+) T cell pool. Additionally, in chronically rejected allograft, the decreased expression of CLEC-1 is associated with a higher production of IL-17. Taken together, our data suggest that CLEC-1, expressed by myeloid cells and endothelial cells, is enhanced by regulatory mediators and moderates Th17 differentiation. Therefore, CLEC-1 may represent a new therapeutic agent to modulate the immune response in transplantation, autoimmunity, or cancer settings.
- Subjects :
- Amino Acid Sequence
Animals
Cell Line
Cells, Cultured
Endothelial Cells pathology
Gene Expression Regulation immunology
Graft Survival genetics
Graft Survival immunology
Heart Transplantation immunology
Heart Transplantation pathology
Immune Tolerance genetics
Inflammation Mediators physiology
Lectins, C-Type antagonists & inhibitors
Lectins, C-Type genetics
Lectins, C-Type physiology
Lymphocyte Activation genetics
Molecular Sequence Data
Rats
Rats, Inbred Lew
T-Lymphocyte Subsets metabolism
Endothelial Cells immunology
Endothelial Cells metabolism
Lectins, C-Type biosynthesis
Lymphocyte Activation immunology
Myeloid Cells immunology
Myeloid Cells metabolism
T-Lymphocyte Subsets immunology
Up-Regulation immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 183
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 19667084
- Full Text :
- https://doi.org/10.4049/jimmunol.0803767