CD84 is a protein found on the surface of various immune cells throughout the body. It functions as a specialized receptor, playing a role in how these cells communicate. This molecule helps coordinate immune responses by facilitating interactions between different immune system components. Understanding CD84’s presence and function offers insights into both healthy immune processes and disease states.
The Role of CD84 in the Immune System
CD84 belongs to the Signaling Lymphocyte Activation Molecule (SLAM) family of proteins, which are clustered together on human chromosome 1. A primary characteristic of CD84 is its ability to act as a self-ligand or homophilic receptor, meaning it binds specifically to other CD84 molecules located on neighboring cells. This self-recognition is fundamental for establishing and maintaining cell-to-cell adhesion between immune cells.
This homophilic binding is important for diverse immune functions, enabling the physical connection and communication necessary for a coordinated response. CD84 functions as a co-receptor, influencing immune responses by either enhancing or suppressing them. Its specific effect depends on the particular immune cell type involved, the cell’s activation state, and the internal signaling pathways that CD84 subsequently triggers. For instance, engaging cell surface CD84 can enhance the secretion of interferon-gamma (IFN-γ) in activated T cells and contribute to platelet stimulation.
Cellular Expression of CD84
CD84 is widely present across many types of immune cells, highlighting its broad importance in immune system coordination. It is expressed on B cells, which produce antibodies, and on T cells, involved in cell-mediated immunity. CD84 is also found on monocytes and dendritic cells, which are antigen-presenting cells that initiate immune responses.
Beyond these, CD84 is expressed on other immune cells such as macrophages, eosinophils, mast cells, and granulocytes. Its presence extends to platelets, small cell fragments involved in blood clotting and immune signaling.
Connection to Autoimmune Disorders
Dysregulation of CD84 signaling has been implicated in the development and progression of various autoimmune disorders. Specific genetic variations in the CD84 gene are associated with diseases like Systemic Lupus Erythematosus (SLE) and rheumatoid arthritis.
In SLE, alterations in CD84-mediated signaling can contribute to immune cell over-activation, leading to inflammation and autoantibody production. Aberrant CD84 function can disrupt the delicate balance required for immune self-recognition. Such imbalances can lead to immune cells mistakenly targeting healthy tissues, driving disease pathology.
Involvement in Cancer
CD84 also plays a role in the context of cancer, particularly in blood cancers. This protein is often found in high abundance on malignant cells in diseases such as Chronic Lymphocytic Leukemia (CLL). In CLL, CD84 signaling contributes to the survival of cancerous B lymphocytes and helps them interact with their microenvironment.
In Multiple Myeloma (MM), CD84 expression is low on malignant cells, but these cells secrete macrophage migration inhibitory factor (MIF). MIF induces high CD84 expression on other cells within the tumor microenvironment, notably myeloid-derived suppressor cells (MDSCs). Activation of CD84 on MDSCs leads to increased expression of programmed death-ligand 1 (PD-L1), which suppresses anti-tumor T cells, allowing cancer to evade immune destruction and thrive.
CD84 as a Therapeutic Target
Given its involvement in both autoimmune dysregulation and cancer survival pathways, CD84 has emerged as a promising target for new therapeutic strategies. The concept behind targeting CD84 is to interfere with its signaling, thereby modulating immune responses or directly affecting cancer cell viability. One approach involves using monoclonal antibodies designed to bind to CD84.
These antibodies could block CD84’s homophilic interactions, disrupting survival signals cancer cells exploit. Alternatively, they might mark malignant cells for immune destruction, or reprogram the tumor microenvironment to become less immunosuppressive. For instance, blocking CD84 has reduced MDSC accumulation, enhanced T cell activity, and decreased tumor burden in preclinical models of multiple myeloma. Research continues to explore the full potential of CD84-targeted therapies in various disease settings.