About this Research Topic
CD24 (also known as heat stable antigen, nectadrin) is a Glycosylphosphatidylinositol (GPI) linked, highly glycosylated, dynamically expressed molecule present on cells of the immune system, myeloid cells, keratinocytes, adipocytes, astrocytes, microglia and neurons.
The biological functions of CD24 cover a very wide spectrum. This would seem to rely on its structural diversity, the nature and extent of glycosylation and a superior ability to co-localize with, and organize, diverse cell surface molecules into lipid rafts associated with signaling pathways. Expression of CD24 is largely differentiation-associated, being most highly expressed at early stages of cell differentiation, such as on early lymphocyte progenitors and during neurogenesis and neuronal regeneration.
In B cell development, CD24 expression is a marker for pre-B cells in fetal liver and bone marrow (BM). Expression remains high on transitional cells exiting the BM, decreases on naïve B cells and is re-expressed on memory B cells, but crucially lost from plasma cells. The signaling properties of CD24 alter during development, being linked to pro-apoptotic pathways in pre-B cells but not later stages. In pre-switch memory B cells, CD24 expression is associated with energy metabolism and the stress response. In primary bone marrow B cells and B cell lines, CD24 increases the release of extracellular vesicles, which are able to transfer competent signaling receptors to recipient B cells.
In the context of malignancy, CD24 expression is widespread, being present in approximately 70% of solid tumors, and often associated with increased metastatic potential and poor prognosis. CD24 is thus a promising biomarker for non-invasive fluorescence imaging, allowing improved tumor resection and as a focus for targeting therapy.
CD24 has also been utilized in a different therapeutic role due to its ability to distinguish self and exogenous molecular patterns. CD24 is a critical regulator of the damage associated molecular pattern (DAMP) response through binding to released self-proteins eg HMGB-1 and heat shock proteins, but not pathogen associated molecular patterns (PAMP). CD24 can co-localize with Sigleg-10 in dendritic cells, resulting in negative signaling. The soluble molecule complexed with Fc fragment of IgG (CD24Fc) has therefore been used to blunt the inflammatory response in contexts such as severe COVID19 infection and autoinflammatory diseases.
While CD24 has been associated with a wide variety of normal and malignant cell types, the mechanisms that underlie its function are less well understood in most cases. For example, the receptor and/or ligand that interacts with and activates CD24 in B cell development or activation has not yet been identified. Furthermore, while targeting of CD24 malignancies using cytotoxic antibodies has been extensively investigated in pre-clinical models, the effect of this treatment on normal, developing B cells, cells of the central nervous system, and others has yet to be determined. Therefore, in this research topic we are calling for articles that can expand the knowledge of CD24 biology, particularly with respect to non-transformed cells as there is less known about these cell types compared to malignant cells, but not exclusively on non-malignant cells.
We welcome the submission of Original Research, Review, Mini-review, and Perspective articles focusing on CD24 biology related to, but not limited to:
- signal transduction
- identification of ligands or receptor partners for CD24
- function in non-malignant cells (eg keratinocytes, adipocytes, neuronal cells, B cells, dendritic cells, etc)
- extracellular vesicle function or identification
- oncology
The biological functions of CD24 cover a very wide spectrum. This would seem to rely on its structural diversity, the nature and extent of glycosylation and a superior ability to co-localize with, and organize, diverse cell surface molecules into lipid rafts associated with signaling pathways. Expression of CD24 is largely differentiation-associated, being most highly expressed at early stages of cell differentiation, such as on early lymphocyte progenitors and during neurogenesis and neuronal regeneration.
In B cell development, CD24 expression is a marker for pre-B cells in fetal liver and bone marrow (BM). Expression remains high on transitional cells exiting the BM, decreases on naïve B cells and is re-expressed on memory B cells, but crucially lost from plasma cells. The signaling properties of CD24 alter during development, being linked to pro-apoptotic pathways in pre-B cells but not later stages. In pre-switch memory B cells, CD24 expression is associated with energy metabolism and the stress response. In primary bone marrow B cells and B cell lines, CD24 increases the release of extracellular vesicles, which are able to transfer competent signaling receptors to recipient B cells.
In the context of malignancy, CD24 expression is widespread, being present in approximately 70% of solid tumors, and often associated with increased metastatic potential and poor prognosis. CD24 is thus a promising biomarker for non-invasive fluorescence imaging, allowing improved tumor resection and as a focus for targeting therapy.
CD24 has also been utilized in a different therapeutic role due to its ability to distinguish self and exogenous molecular patterns. CD24 is a critical regulator of the damage associated molecular pattern (DAMP) response through binding to released self-proteins eg HMGB-1 and heat shock proteins, but not pathogen associated molecular patterns (PAMP). CD24 can co-localize with Sigleg-10 in dendritic cells, resulting in negative signaling. The soluble molecule complexed with Fc fragment of IgG (CD24Fc) has therefore been used to blunt the inflammatory response in contexts such as severe COVID19 infection and autoinflammatory diseases.
While CD24 has been associated with a wide variety of normal and malignant cell types, the mechanisms that underlie its function are less well understood in most cases. For example, the receptor and/or ligand that interacts with and activates CD24 in B cell development or activation has not yet been identified. Furthermore, while targeting of CD24 malignancies using cytotoxic antibodies has been extensively investigated in pre-clinical models, the effect of this treatment on normal, developing B cells, cells of the central nervous system, and others has yet to be determined. Therefore, in this research topic we are calling for articles that can expand the knowledge of CD24 biology, particularly with respect to non-transformed cells as there is less known about these cell types compared to malignant cells, but not exclusively on non-malignant cells.
We welcome the submission of Original Research, Review, Mini-review, and Perspective articles focusing on CD24 biology related to, but not limited to:
- signal transduction
- identification of ligands or receptor partners for CD24
- function in non-malignant cells (eg keratinocytes, adipocytes, neuronal cells, B cells, dendritic cells, etc)
- extracellular vesicle function or identification
- oncology
Keywords: CD24, signal transduction, cellular development, cellular activation, cancer
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