Thymus and activation-regulated chemokine, or TARC (also known as CCL17), is a small protein that acts as a chemical messenger in the body. It belongs to a group of signaling proteins called chemokines, which guide the movement of specific cells. TARC plays a part in the body’s communication network, helping to direct immune cells to certain locations, particularly during inflammation or disease.
Understanding TARC’s Role
TARC’s primary function involves attracting particular types of white blood cells, specifically those that have a receptor called CCR4 on their surface. These include certain CD4+ T cells, such as T helper 2 (Th2) cells and regulatory T cells (Tregs).
TARC acts as a chemotactic factor, meaning it guides these immune cells to specific areas where they are needed, such as sites of inflammation or infection. This directed movement ensures appropriate immune cells arrive where needed to carry out their functions, contributing to the body’s defense. TARC is produced in the thymus and by activated peripheral blood mononuclear cells.
TARC and Immune Responses
TARC’s involvement in the immune system extends beyond simply attracting cells. It plays a role in inflammatory processes, influencing how the immune system responds to various stimuli. The production of TARC can be influenced by other immune signals, such as Interleukin-4 (IL-4). IL-4, a cytokine, can induce TARC expression in various cell types, including human T cells and macrophages.
This induction of TARC by IL-4 highlights its contribution to shaping immune responses, particularly those associated with allergic reactions and T cell-mediated immunity. The interaction between TARC and its receptor CCR4 regulates immune responses, especially in allergic inflammation and immune tolerance. TARC has been linked to the recruitment of Th2 cells to sites of allergic inflammation, contributing to allergic responses. It also attracts CCR4-expressing regulatory T cells (Tregs), which are important for maintaining immune tolerance.
TARC in Diseases
TARC plays a notable role in several diseases, with its levels often altered in these conditions. One such condition is atopic dermatitis, also known as eczema, a chronic inflammatory skin disorder. In atopic dermatitis, TARC levels in the stratum corneum correlate with the severity of local skin lesions, particularly with erythema (redness), edema/papule (swelling/bumps), and oozing/crusts. Serum TARC levels are also closely related to the clinical disease activity of atopic dermatitis.
Another condition where TARC is significant is classical Hodgkin lymphoma, a type of cancer. In this lymphoma, malignant cells, known as Hodgkin and Reed–Sternberg (HRS) cells, produce TARC in high amounts. This TARC helps create a microenvironment that supports the survival and proliferation of HRS cells, primarily by attracting type 2 T helper cells and regulatory T cells. TARC-mediated signaling establishes a positive feedback loop for the interaction between HRS cells and T cells. TARC can be elevated in over 90% of classical Hodgkin lymphoma cases at diagnosis, with median increases of approximately 400 times compared to normal levels.
TARC has also been linked to other allergic and autoimmune conditions. While its role in these conditions may not be as extensively studied as in atopic dermatitis and Hodgkin lymphoma, its ability to attract specific immune cells suggests its involvement in their pathology. Understanding TARC’s role in these diseases helps shed light on their underlying mechanisms and potential interventions.
TARC as a Medical Indicator
TARC levels can be measured in a clinical setting, typically in serum or plasma, using techniques such as enzyme-linked immunosorbent assay (ELISA). This allows TARC to be used as a biomarker, providing insights into a patient’s immune status or disease progression.
In atopic dermatitis, serum TARC levels can serve as a marker for disease activity, correlating with clinical severity scores. Elevated TARC levels can indicate accelerated type 2 inflammation, suggesting the need for intensive therapy to mitigate inflammation. Monitoring TARC levels can also help in assessing the effectiveness of treatments, as a decrease in TARC often aligns with improvement in clinical symptoms.
For classical Hodgkin lymphoma, TARC is a highly validated blood-based biomarker. Elevated TARC levels at diagnosis are associated with known risk factors, and very high levels can predict Hodgkin lymphoma in young patients. During first-line therapy, normalized TARC levels correlate with a negative PET-2 scan and improved progression-free survival. At the end of treatment, higher TARC levels can indicate poorer progression-free survival, even in patients with a negative PET-2 scan.