The ITGAX gene plays a foundational role in the body’s immune system, serving as a blueprint for a specific protein that helps immune cells interact with their environment. This gene’s activity is central to how the body recognizes and responds to threats, whether from foreign invaders or internal abnormalities.
The ITGAX Gene and CD11c Protein
The ITGAX gene codes for a protein called CD11c, also known as Integrin Alpha X or αX Integrin. This gene is conserved across many species, including chimpanzees, dogs, mice, and rats, indicating its fundamental biological importance. The ITGAX gene provides instructions for building the CD11c protein, which is a key component of the immune system.
CD11c is a cell surface protein that forms a larger complex known as an integrin. Specifically, it combines with the beta 2 chain (ITGB2, also known as CD18) to form a heterodimeric integrin complex called CD11c/CD18 or αXβ2 integrin. Integrins are cell adhesion molecules that help cells stick to other cells or to the extracellular matrix. This αXβ2 integrin complex is also referred to as complement receptor 4 (CR4), recognizing activated complement C3 products, like iC3b, which are involved in immune responses.
Cellular Roles of CD11c
CD11c is predominantly found on the surface of several types of immune cells, where it mediates specific functions. It is highly expressed on dendritic cells (DCs), which are often called “professional” antigen-presenting cells due to their ability to initiate immune responses. CD11c is also found on macrophages and monocytes, particularly activated monocytes and alveolar macrophages, though its expression levels can vary. Additionally, certain subsets of natural killer (NK) cells and activated T cells also express CD11c.
The presence of CD11c on these cells facilitates several cellular functions. It plays a role in cell migration, which enables these cells to move through the body to sites of infection or inflammation. CD11c is also involved in phagocytosis, the process by which cells engulf pathogens, cellular debris, or other foreign particles.
CD11c contributes to antigen presentation, particularly by dendritic cells. While CD11c may not be strictly required for all aspects of antigen presentation, it is involved in the uptake of certain cells by dendritic cells, which then process and present antigens to T cells. This interaction helps bridge innate and adaptive immunity, guiding T cell responses towards either activation or tolerance. Furthermore, CD11c mediates cell-to-cell interactions within the immune system, such as those between CD11c-expressing leukocytes and regulatory T cells, influencing immune cell behavior and overall immune responses.
CD11c’s Impact on Immune Responses and Disease
The cellular functions of CD11c contribute significantly to broader immune regulation and have implications for various diseases. CD11c-expressing cells, particularly dendritic cells, are involved in immune surveillance, constantly monitoring the body for threats. Their ability to capture and present antigens helps initiate adaptive immune responses, guiding T cells to respond appropriately to pathogens or abnormal cells. CD11c also influences the resolution of inflammation by contributing to the controlled clearance of cellular debris and the modulation of immune cell activity.
Dysregulation or specific targeting of CD11c is implicated in several conditions. In autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis, increased frequencies of CD11c+ B cells are observed, which are associated with abnormal immune activation. These CD11c+ B cells often show altered expression of markers related to activation and immune checkpoints, suggesting their involvement in the mistaken attack on the body’s own tissues. Targeting CD11c has shown promise in halting the progression of autoimmune conditions such as rheumatoid arthritis and colitis in experimental settings.
In infectious diseases, CD11c-expressing cells are at the forefront of the defense against pathogens, as they are involved in engulfing microbes and presenting their components to other immune cells. Pathogens may also exploit CD11c-expressing cells, influencing infection outcomes. For example, CD11c+ natural killer cells contribute to defense against adenoviral hepatitis. In cancer, CD11c is present on certain tumor-infiltrating immune cells, and its modulation can influence anti-tumor immunity. CD11c expression has been demonstrated to enable complement-dependent cell cytotoxicity towards antibody-coated cancer cells, highlighting its potential as a therapeutic target in cancer immunotherapy. Additionally, CD11c serves as a valuable marker for identifying specific immune cell populations in research and diagnostics, aiding in the study and characterization of various immune-related disorders.