Regulation of myeloid cell function through the CD200 receptor.
Myeloid cells play pivotal roles in chronic inflammatory diseases through their broad proinflammatory, destructive, and remodeling capacities. CD200 is widely expressed on a variety of cell types, while the recently identified CD200R is expressed on myeloid cells and T cells. CD200 deletion in vivo results in myeloid cell dysregulation and enhanced susceptibility to autoimmune inflammation, suggesting that the CD200-CD200R interaction is involved in immune suppression. We demonstrate in this study that CD200R agonists suppress mouse and human myeloid cell function in vitro, and also define a dose relationship between receptor expression and cellular inhibition. IFN-gamma- and IL-17-stimulated cytokine secretion from mouse peritoneal macrophages was inhibited by CD200R engagement. Inhibitory effects were not universal, as LPS-stimulated responses were unaffected. Inhibition of U937 cell cytokine production correlated with CD200R expression levels, and inhibition was only observed in low CD200R expressing cells, if the CD200R agonists were further cross-linked. Tetanus toxoid-induced human PBMC IL-5 and IL-13 secretion was inhibited by CD200R agonists. This inhibition was dependent upon cross-linking the CD200R on monocytes, but not on cross-linking the CD200R on CD4+ T cells. In all, we provide direct evidence that the CD200-CD200R interaction controls monocyte/macrophage function in both murine and human systems, further supporting the potential clinical application of CD200R agonists for the treatment of chronic inflammatory diseases.
Jenmalm
Maria C
MC
SP Biopharma, Palo Alto CA 94022, USA.
Cherwinski
Holly
H
Bowman
Edward P
EP
Phillips
Joseph H
JH
Sedgwick
Jonathon D
JD
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000819:agonists / Q000276:immunology*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; C492346:CD200 receptor, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; C042739:antigens, CD200