CCL17

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signaling proteins). They are found in all vertebrates, some virus species and bacteria. Around 50 chemokines are currently known in humans. 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 their fixed 3-dimensional structure.

In the CC chemokines, the cysteines follow each other directly (see Fig.), in the CXC chemokines they are separated by 1 amino acid (CC = acronym for cysteine-cysteine), in the CXXXC chemokines by 3 other amino acids. Here we show that CCL15 in human synovial fluid are processed by matrix metalloproteinases (MMPs) and serine proteases, produced and secreted by a variety of immune cells. 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 development, homeostasis and proliferation of tissues.

CCL17, also known as C-C motif chemokine ligand 17 or TARC (thymic activity-regulated chemokine) is a small human cytokine belonging to the CC chemokine family. In humans, the coding CCL17 gene is located on chromosome 16 together with the genes for the chemokines CCL22 and CX3CL1. Like CCL22, CCL17 binds to the chemokine receptor CCR4.

Diseases with increased expression of CCL17 are atopic diseases such as:

• atopic dermatitis
• or
• type I-associated food allergies.

Furthermore, increased levels are detected in subcorneal pustulosis, eosinophilic pneumonia and idiopathic pulmonary fibrosis .

Apparently, CCL17 is also expressed non-specifically (by alveolar macrophages); this suggests increased CCL17 levels in chronic smokers.

In children with atopic diseases (inhalative or nutritive type I allergies), a clear correlation between the serum levels of CCL17 and the extent and intensity of the allergic symptoms(SCORAD) was demonstrated.

Arteriosclerosis: CCL17 could be detected in high concentrations in damaged tissue in arteriosclerosis.

CCL17 and carcinomas: CCL17 is very important for the response of the human body to carcinoma development. Some cancers, such as breast cancer, produce CCL17, which attracts T-regulatory cells and thus promotes the cancer's ability to invade. On the other hand, CCL17 also activates tumor-infiltrating lymphocytes. In this respect, in many types of cancer, the more CCL17 is present in the area, the better the prognosis for survival or cure.

CCL17 is discussed together with CXCL9 as a biomarker of GvHD (Chen T et al 2019).

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2. Chen T et al. (2019) The clinical observation of serum specific biomarkers in patients with chronic graft-versus-host disease. Zhonghua Xue Ye Xue Za Zhi 40: 948-952.

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6. Renert-Yuval Y et al. (2021) Biomarkers in atopic dermatitis-a review on behalf of the International Eczema Council". The Journal of Allergy and Clinical Immunology. 147: 1174-1190.

7. Takeuchi S et al. (2015) Incidence, serum IgE and TARC/CCL17 levels in atopic dermatitis associated with other allergic diseases: an update from the Ishigaki cohort. Acta Derm Venereol 95:480-484.
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10. Yogo Y et al. (2009) Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine(CCL17), and CCR4 in idiopathic pulmonary fibrosis. Respir Res 10:80.