CD6 is a protein found on the surface of various immune cells, particularly T-lymphocytes. It helps these cells perceive and react to their surroundings. CD6 plays a role in how T-cells communicate with other cells, influencing their actions within the body’s defense system. Its function is important for maintaining a balanced immune response, protecting the body from foreign invaders while regulating its own reactions.
The Role of CD6 in the Immune System
CD6 functions as a co-stimulatory receptor on T-cells, a type of white blood cell central to adaptive immunity. T-cells require multiple signals for full activation and to carry out their immune functions. CD6 helps provide one of these signals.
CD6 achieves its role through an interaction with CD166, also known as Activated Leukocyte Cell Adhesion Molecule (ALCAM). CD6 on the T-cell binds to CD166 found on other cells, such as antigen-presenting cells (APCs), endothelial cells, and epithelial cells. This binding helps stabilize the connection between T-cells and APCs at the immunological synapse, where T-cells receive activating signals.
The CD6-CD166 interaction is important for regulating the strength and duration of an immune response. It ensures T-cells are activated appropriately to combat infections and other threats. This regulated activation helps prevent the immune system from becoming overly aggressive, which could harm the body’s own tissues.
CD6’s Connection to Autoimmune Diseases
When the CD6 signaling pathway dysfunctions, it contributes to autoimmune diseases. In these conditions, CD6-mediated signaling can become excessive, leading to overactive T-cells. This overactivity causes the immune system to mistakenly target and attack the body’s own healthy tissues.
This dysregulation is observed in conditions such as Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), and Psoriasis. For instance, in MS, overactive T-cells may attack the protective nerve sheaths, while in RA, they can target joint tissues, leading to inflammation and damage. Genetic studies have also linked specific variations in the CD6 gene to susceptibility or changes in disease severity for these autoimmune disorders.
CD6 also guides T-cells, assisting their migration from the bloodstream into tissues where they cause damage. This migration contributes to the localized inflammation and tissue destruction seen in autoimmune conditions, linking CD6 to the harm in affected individuals.
Targeting CD6 for Treatment
Given CD6’s involvement in autoimmune conditions, blocking its function is a therapeutic strategy. This approach aims to calm the overactive immune response characteristic of these diseases. Monoclonal antibodies, laboratory-produced molecules designed to mimic natural antibodies, are used for this purpose.
One such therapeutic antibody is itolizumab, a humanized antibody engineered to bind to CD6. Itolizumab works by attaching to a specific part of the CD6 protein, known as domain 1. By binding to CD6, itolizumab modulates T-cell activation, even though it does not directly prevent CD6 from binding to its partner CD166.
Instead, itolizumab reduces downstream signaling pathways within the T-cell, decreasing T-cell proliferation and the production of pro-inflammatory cytokines, including:
Interferon-gamma (IFN-γ)
Interleukin-6 (IL-6)
Tumor necrosis factor-alpha (TNF-α)
Interleukin-17 (IL-17)
This interruption helps reduce inflammation and T-cell infiltration into affected tissues, managing symptoms and progression of autoimmune diseases like psoriasis and rheumatoid arthritis.
CD6 Beyond the Immune System
While CD6 is primarily recognized for its roles in the immune system, its presence and functions extend to other areas of the body. Research indicates that CD6 is also found on certain types of neurons. In this context, it appears to contribute to the proper development and organization of the nervous system.
Beyond its functions in healthy development, CD6 has been observed on various cancer cells, including those involved in T-cell acute lymphoblastic leukemia (T-ALL), a type of blood cancer. Scientists are investigating CD6 as a potential marker to identify certain cancer cells or as a target for new cancer therapies.