CD23 is a low-affinity IgE receptor that plays a crucial role in regulating IgE production and B cell differentiation. On B cells, it initiates IgE-dependent antigen uptake and presentation to T cells. In macrophages, IgE binding and antigen cross-linking trigger intracellular parasite killing by activating the L-arginine-nitric oxide pathway. CD23 is a C-type lectin. It is present on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets.

Compositional distribution of CD23

There are two forms of CD23: CD23 is initially expressed as a membrane-bound molecule, but it can be cleaved from the cell surface by metalloproteinases such as ADAM-10, generating soluble CD23 fragments (sCD23) of varying molecular weight.

CD23 has two isoforms: CD23a and CD23b. They differ in that the former has 21 amino acids within the cell, while the latter has 22. CD23a is constitutively expressed in B cells, while CD23b requires IL-4 for expression on T cells, monocytes, Langerhans cells, eosinophils, and macrophages. These two isoforms differ in function; for example, CD23a facilitates endocytosis, while CD23b is associated with phagocytosis.

(Data source: W.Cushley, at al. Clinical and Experimental Immunology. 2010)

CD2 3 structure:

CD23 is a trimeric glycoprotein with a molecular weight of approximately 45 kDa and belongs to the calcium-dependent (C-type) lectin family. It consists of a short cytoplasmic N-terminus, a single transmembrane region, and a long C-terminal extracellular domain. The extracellular domain comprises three components: an α-helical coiled stem region, responsible for trimer formation and forming the basis of CD23's molecular structure; a lectin head region, responsible for binding to IgE and a key component of CD23's function as an IgE receptor. Although CD23 is a C-type lectin, its interaction with IgE is not carbohydrate-dependent; and a modified RGD sequence, which binds to α5β5 integrin and participates in cell adhesion and signaling.

(Data source W. Cushley, at al. Clinical and Experimental Immunology. 2010)

CD23 immune mechanism:

A. Regulation of IgE Levels: CD23 can influence IgE levels in the body by binding to IgE. On the surface of B cells, CD23 binding promotes IgE endocytosis and degradation, thereby reducing serum IgE levels. Furthermore, CD23 can influence IgE synthesis through a feedback mechanism, particularly expression on B cells. It can inhibit or promote IgE production, depending on IgE concentration and CD23 activation status.

B. Allergen processing and presentation: CD23 expression on B cells promotes the internalization and processing of IgE-allergen complexes (IgE-ICs). These complexes can be taken up by B cells through CD23-mediated endocytosis and then processed internally by the B cells. The processed allergens can then be delivered by B cells to dendritic cells (DCs), a critical step because DCs are professional antigen-presenting cells that efficiently activate T cells.

C. Immune cell activation: Cross-linking of CD23 can activate B cells and monocytes, leading to the production of inflammatory cytokines and chemokines. These factors can further recruit and activate other immune cells, such as T cells and neutrophils, thereby amplifying the allergic response. In monocytes and DCs, CD23 activation may lead these cells to release pro-inflammatory cytokines, such as TNF-α and IL-1β, which play a key role in allergic reactions.

D. Antigen-specific immune response: CD23-mediated processing and presentation of IgE-ICs can promote antigen-specific T cell activation. This activation may lead to T cell proliferation and differentiation, producing TH2-type cytokines such as IL-4, IL-5, and IL-13, which further promote IgE production and the development of allergic reactions.

(Data source: Paul Engeroff, at al. Allergy. 2021)

Clinical value of CD23:

A. Treatment of allergic diseases: Due to its role in regulating IgE levels and allergic reactions, CD23 has become a potential target for the treatment of allergic diseases. Therapeutic strategies targeting CD23, such as anti-CD23 antibodies, may help alleviate allergic symptoms by reducing IgE-mediated inflammatory responses by inhibiting CD23 function.

B. Immunomodulation: CD23's role in immunomodulation suggests it may play a role in the treatment of autoimmune and inflammatory diseases. By modulating CD23 activity, it may help balance the immune response and prevent excessive inflammation and tissue damage.

C. Treatment of infectious diseases: The role of CD23 in enhancing the pathogen-killing ability of macrophages makes it potentially valuable in the treatment of certain infectious diseases, especially parasitic infections such as leishmaniasis.

D. Cancer Therapy: CD23 is expressed on certain types of cancer cells and may be involved in tumor growth and metastasis. Therefore, CD23 may become a target for certain cancer therapies, limiting tumor development by inhibiting CD23 function.

E. Vaccine Development: Due to the role of CD23 in antigen presentation and T cell activation, it may be considered in vaccine design to enhance vaccine-induced immune responses.

F. Biomarker: In certain disease states, such as chronic lymphocytic leukemia, serum levels of CD23 may be elevated, and thus it can serve as a biomarker of disease activity.

G. Treatment of immunodeficiency diseases: In immunodeficiency diseases, the function of CD23 may be affected, and regulating CD23 may help restore immune balance.

H. Drug development: Research on the structure and function of CD23 will help develop new drugs that can specifically target CD23 for the treatment of related diseases.

The clinical value of CD23 lies in its potential therapeutic role in various diseases and its role as a biomarker for disease diagnosis and monitoring. A deeper understanding and research of CD23 may help develop new treatment strategies and improve clinical outcomes for patients.