Chemokines

Key Biological Properties: CCL5 is a proinflammatory chemokine that recruits leukocytes to sites of inflammation . It is chemotactic for T cells, eosinophils, basophils, monocytes, natural killer (NK) cells, dendritic cells, and mastocytes .

Expression Patterns and Tissue Distribution: CCL5 is mainly expressed by T-cells and monocytes . It is also abundantly expressed by epithelial cells, fibroblasts, and thrombocytes . However, it has not been shown to be expressed by B-cells .

Primary Biological Functions: CCL5 plays a crucial role in recruiting immune cells to sites of inflammation . It is involved in the proliferation and activation of NK cells, forming CC-Chemokine-activated killer (CHAK) cells . Additionally, CCL5 acts as an HIV-suppressive factor released from CD8+ T cells .

Role in Immune Responses and Pathogen Recognition: CCL5 is involved in the homing and migration of effector and memory T cells during acute infections . It also plays a role in antiviral immunity, tumor development, and various human diseases and disorders such as viral hepatitis and COVID-19 .

Mechanisms with Other Molecules and Cells: CCL5 binds to receptors CCR1, CCR3, CCR4, and CCR5, with the highest affinity to CCR5 . Upon binding to CCR5, CCL5 induces the phosphorylation of phosphoinositide 3-kinase (PI3K), which subsequently phosphorylates protein kinase B (PKB/Akt) on serine 473 . The Akt/PKB complex then phosphorylates and inactivates the serine/threonine protein kinase GSK-3 .

Binding Partners and Downstream Signaling Cascades: CCL5 binding to CCR5 leads to the activation of various downstream signaling pathways, including the release of proinflammatory cytokines such as IL-2, IL-5, and IFN-γ .

Regulatory Mechanisms Controlling Expression and Activity: The expression of CCL5 is regulated by Kruppel-like factor 13 (KLF13) in T lymphocytes . The CCL5 gene is activated 3-5 days after T-cell activation via the T-cell receptor (TCR), which is different from most other chemokines that are released almost immediately after cell stimulation . This delayed activation is crucial for maintaining inflammation .

Transcriptional Regulation and Post-Translational Modifications: In fibroblasts and monocytes, rel proteins alone suffice to induce transcription of CCL5 . In T lymphocytes, a molecular complex (enhancesome) including KLF13, rel proteins p50 and p65, and scaffolding proteins is required for CCL5 expression . This complex recruits enzymes involved in acetylation, methylation, and phosphorylation of chromatin .

Biomedical Research: CCL5 is widely used in research to study its role in inflammation, immune responses, and various diseases .

Diagnostic Tools: CCL5 antibodies are used in various diagnostic applications, including ELISA, Western Blot, and Immunohistochemistry .

Therapeutic Strategies: CCL5 is a target for therapeutic strategies aimed at modulating immune responses in diseases such as HIV, cancer, and autoimmune disorders .

Role Throughout the Life Cycle: CCL5 plays a critical role in immune responses throughout the life cycle, from development to aging . It is involved in inflammation maintenance, transplantation, antiviral immunity, and tumor development . High levels of CCL5 are found in the aging stem cell milieu, influencing hematopoietic stem cell subtypes and causing myeloid skewing .