Genes contain the instructions for creating proteins, which carry out nearly every cellular activity. CD103 is a protein with diverse and significant roles within the body, particularly in the immune system.
Understanding CD103
CD103, also known as Integrin alpha E, is a protein found on the surface of certain cells. It is encoded by the Itgae gene, located on chromosome 17 in humans. CD103 belongs to the integrin family of cell surface receptors, which are involved in cell adhesion.
CD103 forms a heterodimeric complex by binding with integrin beta 7 (β7-ITGB7), creating the αEβ7 integrin. This αEβ7 complex is often simply referred to as “CD103,” though the term strictly denotes only the alpha E chain. The αEβ7 integrin functions as a receptor for E-cadherin, a molecule primarily found on epithelial cells, which are cells that line various surfaces and cavities of the body.
CD103’s Role in Immunity and Beyond
CD103 plays a significant role in the immune system, particularly for certain types of T cells and dendritic cells. It is widely expressed on intraepithelial lymphocyte (IEL) T cells, which reside within the epithelial layers of tissues, and on some peripheral regulatory T cells. A subset of dendritic cells found in the gut mucosa and mesenteric lymph nodes also express CD103.
The interaction between CD103 on immune cells and E-cadherin on epithelial cells is a key mechanism for immune surveillance and maintaining tissue integrity. This binding helps immune cells adhere to the epithelial lining of various organs, including the gut, lungs, and skin. This adhesion allows tissue-resident memory T cells (TRM cells) to persistently reside in barrier tissues and rapidly respond to threats. For example, CD103 on cytotoxic T lymphocytes (CTLs) can promote anti-tumor activity by triggering the release of lytic granules upon binding to E-cadherin on tumor cells.
CD103 expression on dendritic cells facilitates their interactions with gastrointestinal epithelia, potentially enhancing mucosal immunosurveillance. In the lungs, CD103+ TRM cells are important for providing immunity against pathogen infection and reinfection. The presence of CD103 on these cells helps prevent their exit from tissues and supports their retention at sites of potential pathogen entry.
CD103 and Health
The presence, absence, or dysregulation of CD103-expressing cells can be linked to various health conditions, including autoimmune diseases and cancers. In inflammatory bowel disease (IBD), a group of autoimmune conditions characterized by chronic intestinal inflammation, CD103’s role is complex and subject to ongoing research. While some studies suggest that CD103 expression on mucosal T cells is associated with IBD disease activity, others indicate that lower percentages of CD103+ T-cell subsets are observed in inflamed biopsies of IBD patients compared to healthy controls.
The ability of CD103 to bind E-cadherin is thought to retain lymphocytes at the epithelial surface, which can influence disease progression in autoimmune contexts. For instance, in some experimental models, blocking CD103 signaling has shown a beneficial role in preventing certain autoimmune conditions. Some research suggests that CD103+CD8+ tissue-resident memory T cells may have a regulatory function in IBD, as they are found in reduced frequencies during active disease and can produce anti-inflammatory cytokines like IL-10.
In the context of cancer, CD103’s role can also be varied depending on the tumor type and microenvironment. In many solid tumors, the presence of CD103+ immune cells, particularly CD8+ tumor-infiltrating lymphocytes (TILs), is associated with a favorable prognosis, including improved overall survival and disease-free survival. These CD103+ TILs are often found preferentially localized to the intraepithelial compartment of tumors and are considered markers of antigen-educated, tumor-specific T cells.
However, in some instances, such as certain colorectal cancer subgroups, high expression of CD103 in normal epithelium has been linked to a poorer prognosis. The co-expression of CD103 with other markers, like CD39, on CD8+ TILs can also indicate highly energetic, tumor-reactive cells that efficiently kill cancer cells. This suggests that CD103+ immune cells contribute to anti-tumor immunity by enhancing T-cell effector functions and improving tumor antigen sensitivity.
CD103 in Medical Research
CD103 is an active area of medical research, with scientists exploring its potential as a biomarker and a therapeutic target. As a biomarker, CD103 expression on immune cells is being investigated for its ability to predict disease diagnosis or prognosis in various cancers. For example, higher frequencies of CD103+CD39+ CD8 TILs are associated with better overall survival in head and neck cancer patients. The density of CD103+ TILs has also been shown to be an independent positive prognostic factor for overall and disease-free survival in esophageal squamous cell carcinoma.
Researchers are also exploring CD103 as a target for new therapies, especially in cancer immunotherapy and for modulating immune responses in autoimmune conditions. For instance, CD103+ dendritic cells are being studied for their role in enhancing responses to immune checkpoint inhibitors in melanoma. Strategies aimed at modulating TGF-β, a cytokine that induces CD103 expression, are being investigated to improve anti-tumor immunotherapies by influencing CD103+ CD8 TRM cell development.
Ongoing research efforts are focused on better understanding the precise mechanisms by which CD103 influences immune cell behavior and disease progression. This includes how CD103 contributes to T-cell activation, migration, and retention in tissues, as well as its interactions with other molecules in the tumor microenvironment. The goal is to leverage this knowledge to develop more targeted and effective treatments for a range of conditions, from solid tumors to inflammatory disorders.