Soluble CD100 functions on human monocytes and immature dendritic cells require plexin C1 and plexin B1, respectively.
CD100 represents the first semaphorin described in the immune system. It is expressed as a 300-kDa homodimer at the surface of most hematopoietic cells, but is also found in a soluble form following a proteolytic cleavage upon cell activation. We herein established that soluble CD100 (sCD100) impaired the migration of human monocytes and immature dendritic cells (DCs), but not of mature DCs. Performing competition assays, we identified plexin C1 (VESPR/CD232) as being involved in sCD100-mediated effects on human monocytes. Interestingly, we observed a complete down-regulation of plexin C1 expression during the in vitro differentiation process of monocytes to immature DCs, while concomitantly the surface expression of plexin B1 was induced. The latter receptor then binds sCD100 on immature DCs, mediating its inhibitory effect on cell migration. Finally, we showed that sCD100 modulated the cytokine production from monocytes and immature DCs. Together these results suggest that sCD100 plays a critical role in the regulation of antigen-presenting cell migration and functions via a tightly regulated process of receptor expression.
Chabbert-de Ponnat
Isabelle
I
INSERM U448, Faculty of Medicine, 8 rue du Général Sarrail, 94010 Créteil Cedex, France.
Marie-Cardine
Anne
A
Pasterkamp
R Jeroen
RJ
Schiavon
Valérie
V
Tamagnone
Luca
L
Thomasset
Nicole
N
Bensussan
Armand
A
Boumsell
Laurence
L
D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D039961:Semaphorins / Q000276:immunology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C093224:CD100 antigen; C064228:CD72 protein, human; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D039961:Semaphorins; C112038:VESPR semaphorin receptor