CCL17

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CCL17
Protein CCL17 PDB 1nr2.png
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesCCL17, A-152E5.3, ABCD-2, SCYA17, TARC, C-C motif chemokine ligand 17
External IDsOMIM: 601520 MGI: 1329039 HomoloGene: 2246 GeneCards: CCL17
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002987

NM_011332

RefSeq (protein)

NP_002978

n/a

Location (UCSC)Chr 16: 57.4 – 57.42 MbChr 8: 94.81 – 94.81 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes.[5] CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response.[6] However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome.[6] CCL17 has also been linked to allergic diseases.[7]

Classification[edit]

CCL17 (CC chemokine ligand 17) was initially named TARC (thymus- and activation-regulated chemokine) when first isolated in 1996.[7] It was later renamed CCL17 as the naming conventions for all cytokines were updated to standardize names.[7]

Function[edit]

Cytokines, like CCL17, help cells communicate with one another, and stimulate cell movement. Chemokines are a type of cytokine that attract white blood cells to sites of inflammation or disease. CCL17 as well as its partner chemokine CCL22 induce chemotaxis in T-helper cells.[5][8][9] They do this by binding to CCR4, a chemokine receptor.[5][8][9] CCL17 is one of the few chemokines that are not stored in the body, except in the thymus; these chemokines are made when needed by dendritic cells, macrophages, and monocytes.[5] CCL17 is expressed constitutively in the thymus, but only transiently in phytohemagglutinin-stimulated peripheral blood mononuclear cells.[8] CCL17 can also be detected in other tissues such as the colon, small intestine, and lung.[7] Granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulates CCL17 production in monocytes and macrophages.[10] Dendritic cells will produce large quantities of CCL17 when stimulated with IL-4 or TSLP.[11][10]

CCL17 was the first CC chemokine identified that interacted with T cells with high affinity.[7] CCL17 was also found to interact with monocytes, but with less affinity. It does not interact with granulocytes.[7] It acts as a powerful chemoattractant to T-helper cells and T-regulatory cells because both can express CCR4.[7][6]

Cancer[edit]

This chemokine is very important in the human body’s response to cancers. While it sometimes allows cancer to invade more rapidly, it more often helps the human body fight cancer.[6] Some cancers that form tumors, such as breast cancer, produce CCL17 which draws T regulatory cells into the area, enhancing the cancer’s ability to invade.[6] On the other hand, CCL17 will also activate tumor-infiltrating lymphocytes tumors.[6] For many cancers, the more CCL17 in the area, the better the prognosis is for cancer survival or recovery.[6]

Inflammation[edit]

Like many cytokines, CCL17 is inflammatory, so while it plays a largely helpful role in attacking cancers, it can induce inflammatory diseases, including allergic skin diseases. Because of its inflammatory effects, much of the medical research is on methods to mitigate CCL17. Neutralizing CCL17 with monoclonal antibodies has been shown to relieve inflammatory arthritis and osteoarthritis.[10] Topical steroids have been found to be an effective tool in normalizing levels of CCL17.[12]

Allergies[edit]

CCL17 sometimes appears to worsen allergic diseases. CCL17 is known to help lymphocytes target areas on the skin, and could play a role in treatment of dermatitis and of other allergic reactions such as asthma.[6] However, CCL17 is thought to trigger several Th2-mediated diseases.[7] Atopic dermatitis(eczema) has been linked to CCL17, especially in infants whose mother does not have the disease.[12] Studies have shown that children with allergies and atopic dermatitis have higher quantiles of CCL17 compared to children without allergies.[12]

Chromosomal location[edit]

In humans the gene for CCL17 is located on chromosome 16 along with other chemokines including CCL22 and CX3CL1.[13][14]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102970 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031780 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d Lacy P (2017). "Eosinophil Cytokines in Allergy". Cytokine Effector Functions in Tissues. Elsevier. pp. 173–218. doi:10.1016/b978-0-12-804214-4.00011-7. ISBN 978-0-12-804214-4.
  6. ^ a b c d e f g h Korbecki J, Kojder K, Simińska D, Bohatyrewicz R, Gutowska I, Chlubek D, Baranowska-Bosiacka I (November 2020). "CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and CCR4". International Journal of Molecular Sciences. 21 (21): 8412. doi:10.3390/ijms21218412. PMID 33182504.
  7. ^ a b c d e f g h Ness TL, Hogaboam CM, Kunkel SL (2006). "Chemokins, CC | TARC (CCL17)". Encyclopedia of Respiratory Medicine. Elsevier. pp. 380–385. doi:10.1016/b0-12-370879-6/00465-8. ISBN 978-0-12-370879-3.
  8. ^ a b c Imai T, Yoshida T, Baba M, Nishimura M, Kakizaki M, Yoshie O (August 1996). "Molecular cloning of a novel T cell-directed CC chemokine expressed in thymus by signal sequence trap using Epstein-Barr virus vector". The Journal of Biological Chemistry. 271 (35): 21514–21. doi:10.1074/jbc.271.35.21514. PMID 8702936.
  9. ^ a b Imai T, Baba M, Nishimura M, Kakizaki M, Takagi S, Yoshie O (June 1997). "The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4". The Journal of Biological Chemistry. 272 (23): 15036–42. doi:10.1074/jbc.272.23.15036. PMID 9169480.
  10. ^ a b c Lee KM, Achuthan AA, Hamilton JA (October 2020). "GM-CSF: A Promising Target in Inflammation and Autoimmunity". ImmunoTargets and Therapy. 9: 225–240. doi:10.2147/itt.s262566. PMID 33150139.
  11. ^ Dembic Z (2015). "Cytokines Important for Growth and/or Development of Cells of the Immune System". The Cytokines of the Immune System. Elsevier. pp. 263–281. ISBN 978-0-12-419998-9.
  12. ^ a b c Furue M (2018-07-25). "T helper type 2 signatures in atopic dermatitis". Journal of Cutaneous Immunology and Allergy. 1 (3): 93–99. doi:10.1002/cia2.12023. ISSN 2574-4593.
  13. ^ Nomiyama H, Imai T, Kusuda J, Miura R, Callen DF, Yoshie O (February 1997). "Assignment of the human CC chemokine gene TARC (SCYA17) to chromosome 16q13". Genomics. 40 (1): 211–3. doi:10.1006/geno.1996.4552. PMID 9070951.
  14. ^ Nomiyama H, Imai T, Kusuda J, Miura R, Callen DF, Yoshie O (1998). "Human chemokines fractalkine (SCYD1), MDC (SCYA22) and TARC (SCYA17) are clustered on chromosome 16q13". Cytogenetics and Cell Genetics. 81 (1): 10–1. doi:10.1159/000015000. PMID 9691168.

Further reading[edit]

External links[edit]