HGNC Approved Gene Symbol: CD24
Cytogenetic location: 6q21 Genomic coordinates (GRCh38): 6:106,969,831-106,976,855 (from NCBI)
The human cell surface antigen CD24 is a sialoglycoprotein that is anchored to the cell surface by a glycosyl phosphatidylinositol (GPI) linkage (Van der Schoot et al., 1989; Fischer et al., 1990). It is expressed in many B-lineage cells and on mature granulocytes. However, studies with monoclonal antibodies indicate that most other hematopoietic cells, including T cells, monocytes, red blood cells, and platelets, seem not to express the CD24 antigen. CD24 has been implicated in both activation and differentiation of B lymphocytes because its expression pattern changes at critical times during B-cell development. Hough et al. (1994) cloned the human CD24 gene.
Using microarray analysis, Jevsek et al. (2006) found that Cd24 was expressed in myofiber synaptic nuclei in embryonic and adult mice.
Aigner et al. (1997) showed that CD24 is a ligand for P-selectin (SELP; 173610) on tumor cells. The major ligand for P-selectin on leukocytes is P-selectin glycoprotein ligand-1 (SELPLG; 600738). The CD24/P-selectin binding pathway could be important in the dissemination of tumor cells by facilitating the interaction with platelets or endothelial cells.
Barkal et al. (2019) demonstrated that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. Barkal et al. (2019) demonstrated a role for tumor-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic acid-binding Ig-like lectin-10 (SIGLEC10; 606091), which is expressed by tumor-associated macrophages. Barkal et al. (2019) found that many tumors overexpress CD24 and that tumor-associated macrophages express high levels of SIGLEC10. Genetic ablation of either CD24 or SIGLEC10, as well as blockade of the CD24-SIGLEC10 interaction using monoclonal antibodies, robustly augmented the phagocytosis of all CD24-expressing human tumors that were tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumor growth in vivo and an increase in survival time. Barkal et al. (2019) concluded that their data revealed CD24 as a highly expressed, antiphagocytic signal in several cancers and demonstrated the therapeutic potential for CD24 blockade in cancer immunotherapy.
Using both somatic cell hybrids and in situ hybridization, Hough et al. (1994) mapped sequences strongly homologous to CD24 to chromosomes 6q21, 15q21-q22, and Yq11. Weaker homologs at 1p36 and on chromosome 20 were also found. PCR and sequence analysis of amplified DNA from the monochromosomal hybrid containing human chromosome 6 indicated that the gene from which the CD24 cDNA is transcribed lies on chromosome 6. While the CD24 gene on the Y chromosome has retained an open reading frame and may be expressed, sequence data indicate that the gene on chromosome 15 is highly unlikely to express a protein similar to CD24 in vivo.
For discussion of a possible association between variation in the CD24 gene and susceptibility to multiple sclerosis, see MS (126200).
Jevsek et al. (2006) found that Cd24-null mice were viable and fertile. Neuromuscular synapses appeared normal in Cd24-null mice, but synaptic transmission was defective. As stimulation frequency increased from 20 to 100 Hz, frequencies typical for the firing rate of fast motor neurons, mutant junctions exhibited periodic bouts of total transmission failure interspersed with periods of transmission but with depressed end-plate potential amplitude. Mutant synapses also showed defects in synaptic vesicle recycling.
Using flow cytometry to analyze T cells transferred into sublethally irradiated (i.e., lymphopenic) wildtype and Cd24 -/- mice, Li et al. (2006) found that T cells divided more rapidly, leading to a greater number of divisions, in Cd24 -/- mice. Cd24 -/- recipient dendritic cells allowed the rapid pace of T-cell homeostatic proliferation, whereas dendritic cells from wildtype mice regulated the slow rate of homeostatic T-cell proliferation in lymphopenic hosts.
Pathogen-associated molecular patterns (PAMPs) and danger (cell injury)-associated molecular patterns (DAMPs) both trigger activation of the innate immune system. Chen et al. (2009) reported that Cd24-deficient mice exhibit increased susceptibility to DAMPs but not PAMPs. CD24 associates with high mobility group box-1 (HMGB1; 163905), heat shock protein-70 (HSP70; 140550), and heat shock protein-90 (HSP90; 140571). CD24 negatively regulates their stimulatory activity and inhibits nuclear factor kappa-B (see 164011) activation. Chen et al. (2009) reported that this occurs at least in part through CD24 association with SIGLEC10 (606091) in humans or SiglecG in mice. Chen et al. (2009) concluded that the CD24-SiglecG pathway protects the host against a lethal response to pathologic cell death and discriminates danger- versus pathogen-associated molecular patterns.
Aigner, S., Sthoeger, Z. M., Fogel, M., Weber, E., Zarn, J., Ruppert, M., Zeller, Y., Vestweber, D., Stahel, R., Sammar, M., Altevogt, P. CD24, a mucin-type glycoprotein, is a ligand for P-selectin on human tumor cells. Blood 89: 3385-3395, 1997. [PubMed: 9129046]
Barkal, A. A., Brewer, R. E., Markovic, M., Kowarsky, M., Barkal, S. A., Zaro, B. W., Krishnan, V., Hatakeyama, J., Dorigo, O., Barkal, L. J., Weissman, I. L. CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature 572: 392-396, 2019. [PubMed: 31367043] [Full Text: https://doi.org/10.1038/s41586-019-1456-0]
Chen, G.-Y., Tang, J., Zheng, P., Liu, Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323: 1722-1725, 2009. [PubMed: 19264983] [Full Text: https://doi.org/10.1126/science.1168988]
Fischer, G. F., Majdic, O., Gadd, S., Knapp, W. Signal transduction in lymphocytic and myeloid cells via CD24, a new member of phosphoinositol-anchored membrane molecules. J. Immun. 144: 638-641, 1990. [PubMed: 2153173]
Hough, M. R., Rosten, P. M., Sexton, T. L., Kay, R., Humphries, R. K. Mapping of CD24 and homologous sequences to multiple chromosomal loci. Genomics 22: 154-161, 1994. [PubMed: 7959762] [Full Text: https://doi.org/10.1006/geno.1994.1356]
Jevsek, M., Jaworski, A., Polo-Parada, L., Kim, N., Fan, J., Landmesser, L. T., Burden, S. J. CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission. Proc. Nat. Acad. Sci. 103: 6374-6379, 2006. [PubMed: 16606832] [Full Text: https://doi.org/10.1073/pnas.0601468103]
Li, O., Chang, X., Zhang, H., Kocak, E., Ding, C., Zheng, P., Liu, Y. Massive and destructive T cell response to homeostatic cue in CD24-deficient lymphopenic hosts. J. Exp. Med. 203: 1713-1720, 2006. [PubMed: 16769998] [Full Text: https://doi.org/10.1084/jem.20052293]
Van der Schoot, C. E., Huizinga, T. W. J., Gadd, S. K., Majdic, O., Wijmans, R., Knapp, W., Von dem Borne, A. E. G. Identification of three novel PI-linked proteins on granulocytes. In: Knapp, W.; Dorken, B.; Gilks, W. R.; Rieber, E. P.; Schmidt, R. E.; Stein, H.; Von dem Borne, A. E. G. K. (eds.): Leukocyte Typing IV: White Cell Differentiation Antigens. Oxford: Oxford Univ. Press (pub.) 1989. Pp. 887-891.