Ccl25

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, some virus types and bacteria. In humans, about 50 chemokines are currently known. A strongly conserved structural feature of all chemokines is a fixed group of cysteine residues that is stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for its fixed 3-dimensional structure.

In the CC chemokines, the cysteines follow each other directly (see figure), in the CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, in the CXXXC chemokines by 3 other amino acids. We show that CCL15 is processed in human synovial fluid by matrix metalloproteinases (MMPs) and serine proteases. They transmit their signals by binding to chemokine receptors via G-proteins. Some chemokines have a pro-inflammatory effect, others have a regulatory effect on the formation, homeostasis and proliferation of tissues.

CCL25, also known as C-C motif chemokine ligand 25, also called TECK or Thymus- Expressed Chemokines, is a small human cytokine belonging to the CC chemokine family. The CCL25 chemokine is formed from a precursor protein consisting of 151 amino acids. CCL25 binds specifically to the receptor CCR9. This chemokine receptor is expressed by thymocytes, macrophages and dendritic cells. The coding gene of CCL25 is located on chromosome 19.

CCL25 plays a role in the development of T cells but also in neoplastic processes.

CCL25 and its chemokine receptor are essential regulators of thymocyte migration and maturation in physiological and inflammatory processes. Thus, the CCR9-CCL25 axis is strikingly expressed in numerous inflammatory and neoplastic processes.

CCL25/malignancies: Chemokine 25 (CCL25) attracts lymphocytes and various tumor cell lines via its chemokine receptor 9 (CCR9). CCR9+ tumor cell lines (breast carcinoma, hepatocellular carcinoma, non-small cell lung carcinoma, ovarian carcinoma). This could affect migration and metastatic behavior of tumor cell lines.

In non-small cell lung car cinoma (NSCLC), CCL25 expression was more pronounced in adenocarcinomas than in squamous cell carcinomas.

Allergic reactions: In murine allograft skin, significant CCR9- overexpression occurs in the spleen of transplant recipients. Neutralization of the CCR9 ligand CCL25 by a monoclonal antibody results in a marked change in allograft survival. This provides evidence for a pathogenetic role of CCL25 in graft rejection reactions. CCL25 induces selective migration of interleukin-17+ gamma/delta T cells and expression of IL-17 in experimentally triggered allergic reactions.

1. Costa MF et al (2012) CCL25 induces α₄β₇ integrin-dependent migration of IL-17⁺ γδ T lymphocytes during an allergic reaction. Eur J Immunol 42:1250-1260.
2. Deng X et al (2017) Wnt5a and CCL25 promote adult T-cell acute lymphoblastic leukemia cell migration, invasion and metastasis. Oncotargetdoi: 10.18632/oncotarget.16559.
3. Gupta P et al (2014) CCR9/CCL25 expression in non-small cell lung cancer correlates with aggressive disease and mediates key steps of metastasis. Oncotarget 5:10170-10179.
4. Li J et al (2013) Anti-CCL25 antibody prolongs skin allograft survival by blocking CCR9 expression and impairing splenic T-cell function. Arch Immunol Ther Exp (Warsz) 61:237-244.
5. Singh R et al (2011) Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer. Int J Oncol 39:373-381.