Expression of CD24 and Siglec-10 in first trimester placenta: implications for immune tolerance at the fetal-maternal interface.

During pregnancy, the fetal-maternal interface establishes immune tolerance between the fetus and the mother. CD24, a mucin-like glycoprotein expressed at the surface of hematopoietic cells and diverse tumor cells, is known to interact with the sialic acid-binding immunoglobulin-type lectins (Siglecs). This interaction was assessed as a candidate complex for the immune suppression response in the placenta. CD24 was affinity purified from term placenta and characterized by SDS-PAGE, Western blot and ELISA. Binding of recombinant Siglecs to placental CD24 was evaluated by ELISA. The expression of CD24 and Siglec-10 in first trimester placental tissues was investigated by immunohistochemistry and immunofluorescence. Placental CD24 had an apparent molecular weight of 30-70 kDa consistent with its high degree of N- and O-linked glycosylation. EDTA-sensitive CD24-Siglec-10 interaction via the terminal sialic acid glycan residues of CD24 was observed. CD24 did not interact with Siglec-3 or Siglec-5. During the first trimester, and already in gestational week (GA) 8, CD24 showed high expression in villous and extravillous cytotrophoblasts. There was also a mild expression in stromal cells, while syncytiotrophoblasts were negative. Co-localization of CD24 with Siglec-10 was observed in endometrial glands and in first trimester decidual cells in close vicinity to extracellular trophoblasts. This study is the first to demonstrate the early presence of CD24 in the placenta cytotrophoblast layers, placental bed and maternal uterine glands. The presence of the CD24-Siglec-10 in these regions of fetal-maternal interactions suggests a possible role in mediating immune tolerance at the fetal-maternal interface.

Glycomic analysis of N-linked carbohydrate epitopes from CD24 of mouse brain.

Murine CD24 is an abundantly glycosylated glycoprotein that plays important roles in the central nervous system and the immune system. It has been proposed that the functions of CD24 are primarily mediated by its N- and/or O-linked glycans. Applying a highly sensitive glycomics approach which included matrix-assisted laser-desorption ionization and electrospray ionization ion trap mass spectrometry, we have performed a detailed analysis of the N-linked glycans of CD24. Our data revealed a highly heterogeneous pattern of mainly complex type glycans expressing distinct carbohydrate epitopes, like 3-linked sialic acid, Le(X) or blood group H antigens, bisecting N-acetylglucosamine residues and N-acetyllactosamine repeats as well as high-mannose and hybrid type species.

Mouse CD24 is required for homeostatic cell renewal.

Under physiological conditions, some adult tissues retain a capacity for self-renewal. This property is attributable to the proliferation and differentiation of stem, transit-amplifying, and differentiating cells, which are regulated by cell-cell or cell-matrix interactions or by secreted factors. By gain and loss of function experiments, we demonstrate the involvement of mouse CD24 (mouse cluster of differentiation 24), which is a glycosyl phosphatidylinositol (GPI)-anchored cell-surface glycoprotein, in the regulation of homeostatic cell renewal. BrdU incorporation observations, at optical and electron-microscopic levels, have revealed increased cell proliferation in the developing brain and in the epithelia of mCD24-deleted mice. We have observed ectopic proliferative cells in the suprabasal layers of the mutant skin leading to a general disruption of basal and suprabasal layers. By contrast, ectopic mCD24 expression mediated by retroviral infection of the embryonic brain leads to a decreased number of clusters of cells generated in the progeny. Together, these results and our previous published data indicate that mCD24 contributes to the regulation of the production of differentiated cells by controlling the proliferation/differentiation balance between transit-amplifying and committed differentiated cells.