Murine Plasmacytoid Dendritic Cells Initiate the Immunosuppressive Pathway of Tryptophan Catabolism in Response to CD200 Receptor Engagement

• Published in: The Journal of immunology (1950) 2004-09, Vol.173 (6), p.3748-3754
• Main Authors: Fallarino, Francesca, Asselin-Paturel, Carine, Vacca, Carmine, Bianchi, Roberta, Gizzi, Stefania, Fioretti, Maria Cristina, Trinchieri, Giorgio, Grohmann, Ursula, Puccetti, Paolo
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Surface - genetics; Antigens, Surface - immunology; Antigens, Surface - metabolism; Binding Sites, Antibody - genetics; Cell Adhesion - genetics; Cell Adhesion - immunology; Cell Line, Tumor; Dendritic Cells - enzymology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dioxygenases; Enzyme Induction - immunology; Female; Immune Tolerance - genetics; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interferon-alpha - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Membrane Proteins; Mice; Mice, Inbred DBA; Mice, Knockout; Orexin Receptors; Oxygenases - biosynthesis; Oxygenases - physiology; Receptor, Interferon alpha-beta; Receptors, Cell Surface; Receptors, Interferon - biosynthesis; Receptors, Interferon - deficiency; Receptors, Interferon - genetics; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; Signal Transduction - genetics; Signal Transduction - immunology; Transfection; Tryptophan - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.6.3748

In this study, using a soluble CD200-Ig fusion protein, we provide evidence that murine dendritic cells (DCs) possess a functional CD200R, whose engagement results in the reinforcement or appearance of immunosuppressive properties in these cells. In particular, the plasmacytoid subset (CD11c+B220+120G8+) of splenic DCs (pDCs) is induced by CD200-Ig to express the enzyme IDO, which initiates the tolerogenic pathway of tryptophan catabolism. As a result, pDCs are capable of suppressing Ag-specific responses in vivo when transferred into recipient hosts after treatment with CD200-Ig. IDO induction in pDCs through CD200R engagement requires type I IFNR signaling. Although the release of IFN-alpha may contribute to the full expression of CD200-Ig activity, autocrine IFN-alpha is unlikely to mediate alone the effects of CD200R engagement. These data prospect novel functions for both pDCs and the CD200-CD200R pair in the mouse. At the same time, these data underscore the possible unifying role of the IDO mechanism in immune tolerance.