The immune system protects the body from illness and infection. Signaling Lymphocytic Activation Molecule Family member 6, or SLAMF6, plays a significant part in this complex defense network. Understanding SLAMF6’s actions helps to clarify how the immune system maintains health and responds to various threats.
What is SLAMF6
SLAMF6 is a cell surface receptor protein found on immune cells. It is also known by other names such as CD352, KALI, KALIb, Ly108, NTB-A, and NTBA. This protein is part of the SLAM family of receptors, which are involved in regulating how immune cells interact and become activated. SLAMF6 functions as a signaling molecule, facilitating communication within the immune system. It is a type I transmembrane protein, meaning it spans the cell membrane.
SLAMF6 is predominantly expressed on various immune cells, including T lymphocytes, B lymphocytes, and natural killer (NK) cells. Its structure includes two extracellular immunoglobulin-like domains and three cytoplasmic tyrosine-based signaling motifs. When activated, SLAMF6 undergoes tyrosine phosphorylation and can associate with specific proteins like SH2D1A (SLAM-associated protein, or SAP) and SH2 domain-containing phosphatases (SHPs), which are crucial for transmitting signals inside the cell.
How SLAMF6 Influences Immune Responses
SLAMF6 plays a dual role in modulating immune cell activity, capable of both enhancing and inhibiting immune responses to maintain balance within the immune system. Its influence is particularly notable on T cells and Natural Killer (NK) cells. SLAMF6 is constitutively expressed on T cells, and its expression increases when these cells are activated.
On T cells, SLAMF6 can influence their activation, proliferation, and differentiation. For instance, it contributes to positive regulation of interferon-gamma and interleukin-17 production, which are important signaling molecules in immune responses. In some contexts, SLAMF6 acts as an inhibitory checkpoint receptor, meaning its presence can limit T cell activity, preventing an overactive immune response.
SLAMF6 also functions as a co-receptor in the activation of NK cells. It can mediate inhibitory signals in NK cells. The precise signaling pathways influenced by SLAMF6 involve intracellular molecules like SAP and EAT-2, which are adapter proteins that transmit signals from the receptor into the cell. The balance between SAP and SHP-1 binding to SLAMF6 dictates whether it sends positive or negative signals, thus regulating T cell function and NKT cell development.
SLAMF6’s Role in Disease
Dysfunction or dysregulation of SLAMF6 can contribute to various disease states, impacting the body’s ability to fight illness or leading to immune system overactivity. In cancer, altered SLAMF6 activity is linked to the development and progression of certain malignancies. For example, studies suggest that suppressing SLAMF6 on killer T cells can increase their activity, potentially helping to treat cancers such as melanoma skin cancers. The absence of SLAMF6 in CD8+ T cells has been shown to improve anti-melanoma activity and more effectively prevent tumor growth.
In autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues, SLAMF6 dysregulation can lead to immune overactivity. An example is systemic lupus erythematosus, where an imbalance in SLAMF6 function may contribute to the immune system’s uncontrolled responses. The ability of SLAMF6 to either enhance or inhibit immune responses means that its inappropriate activity can disrupt the delicate balance needed to prevent autoimmune conditions.
SLAMF6 also plays a role in influencing immune responses to pathogens, which can affect susceptibility or severity of infectious diseases. For instance, it can bind to components of bacteria and viruses. These interactions can impact NK cell cytotoxicity, demonstrating its involvement in the immune system’s response to both bacterial and viral infections.
Exploring SLAMF6 for Therapies
Understanding the mechanisms of SLAMF6 in both healthy and diseased states is opening new avenues for developing therapeutic strategies. Researchers are exploring how targeting SLAMF6 could modulate immune responses to treat various conditions, including cancer and autoimmune disorders. This involves developing agents, such as small molecules, antibodies, or other biologics, designed to interact with SLAMF6 receptors on immune cell surfaces.
These agents, known as SLAMF6 modulators, can either enhance or inhibit the signaling pathways associated with SLAMF6. For example, SLAMF6 agonists could stimulate T cells and NK cells to improve their ability to recognize and destroy cancer cells. Conversely, SLAMF6 antagonists could dampen an overactive immune response. Preclinical studies have shown that SLAMF6 modulation can lead to enhanced anti-tumor activity and improved survival rates in animal models, highlighting its potential as a future medical target.