CD103 is a protein marker found on the surface of certain immune cells. As an integrin, it facilitates cell adhesion, enabling cells to stick to other cells or to the surrounding environment. CD103 influences how immune cells interact with and move within tissues, directing the immune response to specific locations.
The Role of CD103 in the Immune System
CD103 is known as an alpha E integrin (αE integrin), and it forms a pair with another integrin subunit called beta 7 (β7). This αEβ7 integrin complex binds to E-cadherin, a protein commonly found on the surface of epithelial cells. Epithelial cells form protective layers, such as those lining the skin, lungs, and gut.
This binding mechanism allows immune cells, including certain T cells and dendritic cells, to interact with and navigate these specific tissues. By binding to E-cadherin, CD103 helps anchor immune cells, allowing them to survey the tissue environment and respond to threats.
CD103 and Tissue-Resident Memory T Cells
CD103 is a defining marker for many Tissue-Resident Memory T (TRM) cells, which are long-lived immune cells that stay in specific tissues like the skin, lungs, and gastrointestinal tract. These cells provide immediate protection against pathogens the body has encountered before. TRM cells are distinct from other memory T cells that circulate through the blood and lymph.
CD103’s ability to bind to E-cadherin on epithelial cells helps TRM cells remain in and persist within these tissues. This adhesion allows TRM cells to maintain close contact with the tissue environment, ready to respond quickly to a re-infection at the site of entry. The formation and maintenance of CD103 expressing TRM cells are influenced by cytokines like TGF-β, which upregulates CD103 expression, and transcription factors such as Runx3.
TRM cells contribute to local immunity by acting as an immunosurveillance population within the tissue. When reactivated, oral TRM cells can trigger changes in gene expression related to somatosensation and innate immunity. The presence of CD103 facilitates a strong connection between these cytotoxic T cells and target cells, enhancing the release of cytotoxic molecules and improving the killing of infected or cancerous cells.
CD103’s Significance in Health and Disease
The understanding of CD103 has practical implications in various health and disease contexts. As a diagnostic marker, CD103 expression on immune cells, particularly T cells, can indicate certain conditions. For instance, increased CD103-positive T cells are implicated in tissue damage in autoimmune conditions like celiac disease. In some cancers, the presence of CD103-positive tumor-infiltrating lymphocytes (TILs) is associated with a favorable prognosis and improved overall survival.
CD103 also presents a potential target for therapeutic interventions. In cancer immunotherapy, modulating CD103-positive cells can enhance anti-tumor responses. For example, CD103 expression on cancer-reactive T cells increases during successful immunotherapy, making it a potential biomarker for treatment effectiveness.
In autoimmune diseases, targeting CD103 could help reduce inflammation. Antibody-drug conjugates (ADCs) designed to target CD103 are being explored to selectively eliminate pathogenic T cells involved in autoimmune disorders. Further research is ongoing to fully understand its therapeutic potential in diverse disease settings.