Biology:C-C chemokine receptor type 6

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Short description: Mammalian protein found in Homo sapiens

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene.[1] CCR6 has also recently been designated CD196 (cluster of differentiation 196). The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids (molecular weight 42,494 Da).[1]

Function

This protein belongs to family A of G protein-coupled receptor superfamily. The gene is expressed in lymphatic and non-lymphatic tissue as spleen, lymph nodes, pancreas, colon, appendix, small intestine. CCR6 is expressed on B-cells, immature dendritic cells (DC), T-cells (Th1, Th2, Th17, Treg), natural killer T cells (NKT cells) and neutrophils.[2] The ligand of this receptor is CCL20 or in the other name - macrophage inflammatory protein 3 alpha (MIP-3 alpha). This chemokine receptor is special because it binds only one chemokine ligand CCL20 in comparison to other chemokine receptors.[3] CCR6 has a key role between immature DC and adaptive immunity.[4] This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may regulate the migration and recruitment of dendritic cells and T cells during inflammatory and immunological responses. Alternatively spliced transcript variants that encode the same protein have been described for this gene.[5]

Interleukin 4 (IL-4) and interferon gamma (IFNγ) suppress expression of CCR6 in langerhans cells development and interleukin 10 (IL-10) induces the expression. It can regulate immune response in inflammatory tissue.[6]

Proinflammatory Th17 cells express CCR6 and its ligand CCL20. CCR6 influences their migration to sites of inflammation. Some Th17 cells migrate via chemokine gradient of CCL20 to inflammatory sites and themselves can express more CCL20 to bring in more Th17 cells and regulatory T-cells (Treg). This can lead to chronic inflammation. In some models, the lack of CCR6 leads to less severe autoimmune encephalomyelitis.[7]

Clinical significance

CCR6 has a function in development and metastatic spread of gastrointestinal malignancies.[3] Expression of CCR6 was found to be up-regulated in colorectal cancer.[8] Many patients with colorectal cancer have liver metastases. Colorectal carcinoma cells express CCR6 and CCL20. High level of CCL20 in liver chemoattract colorectal carcinoma cells and cause metastases in liver.[3][9] Novel research has identified a microRNA that is able to downregulate CCR6 in cancer cell lines.[10]

CCR6 has been associated with Crohn's disease.[11]

References

  1. ↑ 1.0 1.1 "Molecular cloning and RNA expression of two new human chemokine receptor-like genes". Biochemical and Biophysical Research Communications 227 (3): 846–853. October 1996. doi:10.1006/bbrc.1996.1595. PMID 8886020. Bibcode: 1996BBRC..227..846Z. 
  2. ↑ "The CC chemokine CCL20 and its receptor CCR6". Cytokine & Growth Factor Reviews 14 (5): 409–426. October 2003. doi:10.1016/s1359-6101(03)00049-2. PMID 12948524. 
  3. ↑ 3.0 3.1 3.2 "Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview". World Journal of Gastroenterology 22 (2): 833–841. January 2016. doi:10.3748/wjg.v22.i2.833. PMID 26811629. 
  4. ↑ "Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites". The Journal of Experimental Medicine 188 (2): 373–386. July 1998. doi:10.1084/jem.188.2.373. PMID 9670049. 
  5. ↑ "Entrez Gene: CCR6 chemokine (C-C motif) receptor 6". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1235. 
  6. ↑ "IL-10 induces CCR6 expression during Langerhans cell development while IL-4 and IFN-gamma suppress it". Journal of Immunology 167 (10): 5594–5602. November 2001. doi:10.4049/jimmunol.167.10.5594. PMID 11698430. 
  7. ↑ "CCR6 regulates the migration of inflammatory and regulatory T cells". Journal of Immunology 181 (12): 8391–8401. December 2008. doi:10.4049/jimmunol.181.12.8391. PMID 19050256. 
  8. ↑ "Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells". Journal of Translational Medicine 12: 48. February 2014. doi:10.1186/1479-5876-12-48. PMID 24559209. 
  9. ↑ "CCR6/CCL20 chemokine expression profile in distinct colorectal malignancies". Scandinavian Journal of Immunology 78 (3): 298–305. September 2013. doi:10.1111/sji.12087. PMID 23790181. 
  10. ↑ "Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells". Journal of Translational Medicine 12: 48. February 2014. doi:10.1186/1479-5876-12-48. PMID 24559209. 
  11. ↑ "Diverse genome-wide association studies associate the IL12/IL23 pathway with Crohn Disease". American Journal of Human Genetics 84 (3): 399–405. March 2009. doi:10.1016/j.ajhg.2009.01.026. PMID 19249008. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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