Chemokines

Key Biological Properties: MDC/CCL22 is a chemokine that exhibits chemotactic activity, meaning it can attract immune cells to specific locations. It is particularly effective in attracting cells that express the CCR4 receptor .

Expression Patterns: MDC/CCL22 is predominantly expressed in dendritic cells, macrophages, and activated T-cells. It is also found in various tissues, including the thymus, lymph nodes, and spleen .

Tissue Distribution: High levels of MDC/CCL22 expression are observed in the thymus, where it plays a role in T-cell maturation. It is also present in the lungs, spleen, and other lymphoid tissues .

Primary Biological Functions: MDC/CCL22 is primarily involved in the regulation of immune responses. It recruits T-lymphocytes, particularly regulatory T cells (Tregs), to sites of inflammation or infection. This recruitment is essential for maintaining immune homeostasis and preventing excessive inflammatory responses .

Role in Immune Responses: MDC/CCL22 plays a critical role in modulating immune responses by attracting Tregs, which help suppress immune reactions and maintain tolerance to self-antigens. It is also involved in pathogen recognition and the initiation of immune responses against infections .

Mechanisms with Other Molecules and Cells: MDC/CCL22 exerts its effects by binding to the CCR4 receptor on target cells. This binding triggers a series of intracellular signaling cascades that lead to the migration and activation of these cells .

Binding Partners: The primary binding partner of MDC/CCL22 is the CCR4 receptor, which is expressed on Tregs, Th2 cells, and other immune cells .

Downstream Signaling Cascades: Upon binding to CCR4, MDC/CCL22 activates downstream signaling pathways, including the ERK1/2 and PI3K/Akt pathways. These pathways are involved in cell migration, survival, and activation .

Transcriptional Regulation: The expression of MDC/CCL22 is regulated at the transcriptional level by various cytokines and transcription factors. For example, IL-4 and IL-13 can upregulate its expression, while IFN-γ can downregulate it .

Post-Translational Modifications: MDC/CCL22 can undergo post-translational modifications, such as glycosylation, which can affect its stability and activity .

Biomedical Research: MDC/CCL22 is widely used in research to study immune cell migration and the mechanisms of immune regulation. It is also used as a marker for certain types of immune cells .

Diagnostic Tools: Elevated levels of MDC/CCL22 can be indicative of certain inflammatory conditions and diseases, making it a potential biomarker for diagnostic purposes .

Therapeutic Strategies: Targeting the MDC/CCL22-CCR4 axis has therapeutic potential in treating autoimmune diseases, allergies, and cancer. Inhibitors of MDC/CCL22 or its receptor CCR4 are being explored as potential treatments for these conditions .

Development: During development, MDC/CCL22 plays a role in the maturation and migration of T-cells in the thymus .

Aging: The expression and function of MDC/CCL22 can change with age, potentially affecting immune responses in older individuals .

Disease: Dysregulation of MDC/CCL22 has been implicated in various diseases, including autoimmune disorders, allergies, and cancer. Its role in recruiting Tregs to the tumor microenvironment can contribute to immune evasion by tumors .