CD24: from a Hematopoietic Differentiation Antigen to a Genetic Risk Factor for Multiple Autoimmune Diseases

Abstract

The autoantibody is an essential characteristic of inflammatory disorders, including autoimmune diseases. Although the exact pathogenic mechanisms of these diseases remain elusive, accumulated evidence has implicated that genetic factors play important roles in autoimmune inflammation. Among these factors, CD24 was first identified as a heat-stable antigen in 1978 and first successfully cloned in 1990. Thereafter, its functional roles have been intensively investigated in various human diseases, especially autoimmune diseases and cancers. It is currently known that CD24 serves as a costimulatory factor of T cells that regulate their homeostasis and proliferation, while in B cells, CD24 is functionally involved in cell activation and differentiation. CD24 can enhance autoimmune diseases in terms of its protective role in the clonal deletion of autoreactive thymocytes. Furthermore, CD24 deficiency has been linked to mouse experimental autoimmune encephalomyelitis. Finally, CD24 genetic variants, including single-nucleotide polymorphisms and deletions, are etiologically relevant to autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus. Therefore, CD24 is a promising biomarker and novel therapeutic target for autoimmune diseases.

Analysis of the structure, evolution, and expression of CD24, an important regulator of cell fate

“…The CD24 gene has been well characterized in both the mouse and human systems at the functional and genomic level (Tan et al, 2016), however, very little is known about CD24 in other species. CD24 homologue sequences, which were generally annotated as CD24 or CD24-like (CD24L) with predicted genes given either designation, were analyzed.…”

“…3.3. Dynamic regulation of CD24 gene expression and its putative ligands during cellular development CD24 is dynamically regulated throughout development at the mRNA and protein levels in multiple cell types (Fang et al, 2010;Smith et al, 2015;Tan et al, 2016;Jeffery et al, 2015), in addition to being highly expressed in the developing embryo (Shirasawa et al, 1993). Multiple ligands for CD24 have been identified, which interact with CD24 either in cis or in trans.…”

“…4B), and DCs (Fig. 4C), in which CD24 is known to positively regulate apoptosis, homeostatic proliferation, and repression of activation, respectively (Tan et al, 2016).…”

“…Cleavage of the N-terminal signal sequence and C-terminal glycophosphatidylinositol (GPI)-anchor sequence results in a mature peptide of 27 residues in mouse and 32 residues in humans (Kay et al, 1991). The mature, GPI-anchored CD24 peptide is also post-translationally modified with N-and O-linked glycosylations leading to a final molecular mass between 20 and 70 kDa (Fang et al, 2010) The mature surface protein has roles in regulating the development of many different cell types including B lymphocytes (B cells), T lymphocytes (T cells), neuronal cells, adipocytes, colon crypt cells, and epithelial cells in the mammary gland (Fang et al, 2010;Smith et al, 2015;Tan et al, 2016). In addition, CD24 contributes to T cell and dendritic cell (DC) activation, as well as regulating the proliferation of many different cancer cell types including pancreas, lung, colorectal, and breast (Kristiansen et al, 2004).…”

“…In addition, CD24 contributes to T cell and dendritic cell (DC) activation, as well as regulating the proliferation of many different cancer cell types including pancreas, lung, colorectal, and breast (Kristiansen et al, 2004). It has also been shown in many cell types that CD24 mRNA and protein expression are dynamic and associated with cell maturation or development where CD24 is highly expressed on developing cells with little to no expression in mature cell stages (Tan et al, 2016). This was first characterized in mouse B cells, where CD24 was used as a marker for early, progenitor and precursor B cell stages (Hardy et al, 1991).…”