title: 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.
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.
authors: INSERM, Unité 643, Institut de Transplantation et de Recherche en Transplantation, Centre Hospitalier Universitaire de Nantes, Nantes, France.
authors: Pamela
authors: P
authors: Thebault
authors: Natacha
authors: N
authors: Lhermite
authors: Gaëlle
authors: G
authors: Tilly
authors: Laëtitia
authors: L
authors: Le Texier
authors: Thibaut
authors: T
authors: Quillard
authors: Michele
authors: M
authors: Heslan
authors: Ignacio
authors: I
authors: Anegon
authors: Jean-Paul
authors: JP
authors: Soulillou
authors: Sophie
authors: S
authors: Brouard
authors: Beatrice
authors: B
authors: Charreau
authors: Maria-Cristina
authors: MC
authors: Cuturi
authors: Elise
authors: E
authors: Chiffoleau
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000235:genetics; D018836:Inflammation Mediators / Q000502:physiology; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
chemical_list: C543376:CLEC-1 protein, rat; D018836:Inflammation Mediators; D037181:Lectins, C-Type