Mobilizing dendritic cells for tolerance by engagement of immune inhibitory receptors for HLA-G.
The presence of dendritic cells (DC) in the maternal decidua has pointed to a biologic role of antigen-presenting cell in maternal-fetal interaction. The expression of immune inhibitory receptors on DC opens the intriguing possibility that these types of receptors are directly involved in maturation/activation of DC and modulate their function. We show that the triggering of the murine inhibitory receptor paired immunoglobulin-like receptor-B by cross-linking or by human leukocyte antigen (HLA)-G tetramer resulted in the modulation of DC function and prolongation of allogeneic graft survival. In addition, we found that the engagement of human inhibitory receptor ILT4 by its natural ligand, HLA-G, alters maturation of human DC. In this study, we examined the mechanisms for the modulation of antigen-presenting cells by HLA-G. These findings have established an important link between HLA-G and immune inhibitory receptor regulation in vivo and in vitro, thereby placing HLA-G in the inhibitory pathway.
Liang
Siyuan
S
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Horuzsko
Anatolij
A
D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D016038:Skin Transplantation / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D023201:CD40 Ligand; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse