C-C chemokine receptor type 7
(Redirected from
CCR7
)Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 17: 40.55 – 40.57 Mb | Chr 11: 99.04 – 99.05 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene.[5] Two ligands have been identified for this receptor: the chemokines (C-C motif) ligand 19 (CCL19/ELC) and (C-C motif) ligand 21 (CCL21).[6] The ligands have similar affinity for the receptor, though CCL19 has been shown to induce internalisation of CCR7 and desensitisation of the cell to CCL19/CCL21 signals.[7] CCR7 is a transmembrane protein with 7 transmembrane domains, which is coupled with heterotrimeric G proteins, which transduce the signal downstream through various signalling cascades. The main function of the receptor is to guide immune cells to immune organs (lymph nodes, thymus, spleen) by detecting specific chemokines, which these tissues secrete.[7]
CCR7 has also recently been designated CD197 (cluster of differentiation 197).
Function
The protein encoded by this gene is a member of the
B lymphocytes.[8] As stated above, the receptor guides immune cells to immune organs such as lymph nodes, which is needed for the development of both resistance and tolerance, but it is also important for development of T cells in thymus. The receptor is expressed mostly on adaptive immune cell types, namely thymocytes, naive T and B cells, regulatory T cells, central memory lymphocytes, but also dendritic cells.[7] CCR7 has been shown to stimulate dendritic cell maturation. CCR7 is also involved in homing of T cells to various secondary lymphoid organs such as lymph nodes and the spleen as well as trafficking of T cells within the spleen.[8]
CCR7 in dendritic cells
CCR7´s function is best studied in dendritic cells. Their activation in peripheral tissues induces CCR7 expression on the cell's surface, which recognize
4EBP1. CCR7 affects cellular actin dynamics via the RhoA/cofilin pathway.[10]
Influence of CCR7 on central tolerance
CCR7 has been shown to be important for the selection process of
dendritic cells to lymph nodes.[11]
Clinical significance
CCR7 is expressed by various cancer cells, such as nonsmall lung cancer, gastric cancer and oesophageal cancer.[12][13][14] Expression of CCR7, usually with VEGF family proteins, by cancer cells is linked with metastasis and generally poorer prognosis.[15] Multiple mechanisms through which CCR7 expression changes the prognosis of cancer patients have been discovered.[16] As described above on the example of dendritic cells, CCR7 enhances survival of the cell and enables it to migrate following CCL19/CCL21 gradient, which leads to lymph nodes, in addition to that it has been shown that CCR7 ligation promotes EMT transition, which is cruicial for metastasis, as it allows cells to detach and migrate. Also CCR7 signalling induces VEGF-C and VEGF-D molecules, which promote lymphoneogenesis around the tumour.[16]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000126353 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037944 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8383238.
- ^ F. Balkwill, Cancer and the Chemokine Network, Nature reviews, 2004
- ^ PMID 35874608.
- ^ PMID 26500349.
- PMID 15778365.
- ^ PMID 32351499.
- PMID 34361107.
- PMID 12019175.
- S2CID 1523901.
- PMID 12960129.
- PMID 17560334.
- ^ S2CID 230108218.
External links
- Human CCR7 genome location and CCR7 gene details page in the UCSC Genome Browser.
Further reading
- Müller G, Lipp M (June 2003). "Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking". Microcirculation. 10 (3–4): 325–334. S2CID 1785143.
- Burgstahler R, Kempkes B, Steube K, Lipp M (October 1995). "Expression of the chemokine receptor BLR2/EBI1 is specifically transactivated by Epstein-Barr virus nuclear antigen 2". Biochemical and Biophysical Research Communications. 215 (2): 737–743. PMID 7488016.
- Schweickart VL, Raport CJ, Godiska R, Byers MG, Eddy RL, Shows TB, Gray PW (October 1994). "Cloning of human and mouse EBI1, a lymphoid-specific G-protein-coupled receptor encoded on human chromosome 17q12-q21.2". Genomics. 23 (3): 643–650. PMID 7851893.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. PMID 8889548.
- Yoshida R, Imai T, Hieshima K, Kusuda J, Baba M, Kitaura M, et al. (May 1997). "Molecular cloning of a novel human CC chemokine EBI1-ligand chemokine that is a specific functional ligand for EBI1, CCR7". The Journal of Biological Chemistry. 272 (21): 13803–13809. PMID 9153236.
- Yoshida R, Nagira M, Kitaura M, Imagawa N, Imai T, Yoshie O (March 1998). "Secondary lymphoid-tissue chemokine is a functional ligand for the CC chemokine receptor CCR7". The Journal of Biological Chemistry. 273 (12): 7118–7122. PMID 9507024.
- Campbell JJ, Bowman EP, Murphy K, Youngman KR, Siani MA, Thompson DA, et al. (May 1998). "6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3beta receptor CCR7". The Journal of Cell Biology. 141 (4): 1053–1059. PMID 9585422.
- Kim CH, Pelus LM, White JR, Broxmeyer HE (September 1998). "Macrophage-inflammatory protein-3 beta/EBI1-ligand chemokine/CK beta-11, a CC chemokine, is a chemoattractant with a specificity for macrophage progenitors among myeloid progenitor cells". Journal of Immunology. 161 (5): 2580–2585. S2CID 255361893.
- Yanagihara S, Komura E, Nagafune J, Watarai H, Yamaguchi Y (September 1998). "EBI1/CCR7 is a new member of dendritic cell chemokine receptor that is up-regulated upon maturation". Journal of Immunology. 161 (6): 3096–3102. S2CID 26084149.
- Hasegawa H, Nomura T, Kohno M, Tateishi N, Suzuki Y, Maeda N, et al. (January 2000). "Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells". Blood. 95 (1): 30–38. PMID 10607681.
- Gosling J, Dairaghi DJ, Wang Y, Hanley M, Talbot D, Miao Z, Schall TJ (March 2000). "Cutting edge: identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK". Journal of Immunology. 164 (6): 2851–2856. PMID 10706668.
- Agace WW, Roberts AI, Wu L, Greineder C, Ebert EC, Parker CM (March 2000). "Human intestinal lamina propria and intraepithelial lymphocytes express receptors specific for chemokines induced by inflammation". European Journal of Immunology. 30 (3): 819–826. PMID 10741397.
- Annunziato F, Romagnani P, Cosmi L, Beltrame C, Steiner BH, Lazzeri E, et al. (July 2000). "Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and are produced by distinct subsets of medullary epithelial cells: possible implications for negative selection". Journal of Immunology. 165 (1): 238–246. PMID 10861057.
- Campbell JJ, Murphy KE, Kunkel EJ, Brightling CE, Soler D, Shen Z, et al. (January 2001). "CCR7 expression and memory T cell diversity in humans". Journal of Immunology. 166 (2): 877–884. PMID 11145663.
- Campbell JJ, Qin S, Unutmaz D, Soler D, Murphy KE, Hodge MR, et al. (June 2001). "Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire". Journal of Immunology. 166 (11): 6477–6482. PMID 11359797.
- Taylor JR, Kimbrell KC, Scoggins R, Delaney M, Wu L, Camerini D (September 2001). "Expression and function of chemokine receptors on human thymocytes: implications for infection by human immunodeficiency virus type 1". Journal of Virology. 75 (18): 8752–8760. PMID 11507220.
- Höpken UE, Foss HD, Meyer D, Hinz M, Leder K, Stein H, Lipp M (February 2002). "Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocyte-predominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs". Blood. 99 (4): 1109–1116. PMID 11830455.
- Nakayama T, Fujisawa R, Izawa D, Hieshima K, Takada K, Yoshie O (March 2002). "Human B cells immortalized with Epstein-Barr virus upregulate CCR6 and CCR10 and downregulate CXCR4 and CXCR5". Journal of Virology. 76 (6): 3072–3077. PMID 11861876.
- Till KJ, Lin K, Zuzel M, Cawley JC (April 2002). "The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes". Blood. 99 (8): 2977–2984. PMID 11929789.
- Sánchez-Sánchez N, Riol-Blanco L, de la Rosa G, Puig-Kröger A, García-Bordas J, Martín D, et al. (August 2004). "Chemokine receptor CCR7 induces intracellular signaling that inhibits apoptosis of mature dendritic cells". Blood. 104 (3): 619–625. PMID 15059845.
- López-Cotarelo P, Escribano-Díaz C, González-Bethencourt IL, Gómez-Moreira C, Deguiz ML, Torres-Bacete J, et al. (January 2015). "A novel MEK-ERK-AMPK signaling axis controls chemokine receptor CCR7-dependent survival in human mature dendritic cells". The Journal of Biological Chemistry. 290 (2): 827–840. PMID 25425646.
- Riol-Blanco L, Sánchez-Sánchez N, Torres A, Tejedor A, Narumiya S, Corbí AL, et al. (April 2005). "The chemokine receptor CCR7 activates in dendritic cells two signaling modules that independently regulate chemotaxis and migratory speed". Journal of Immunology. 174 (7): 4070–4080. PMID 15778365.
- Torres-Bacete J, Delgado-Martín C, Gómez-Moreira C, Simizu S, Rodríguez-Fernández JL (August 2015). "The Mammalian Sterile 20-like 1 Kinase Controls Selective CCR7-Dependent Functions in Human Dendritic Cells". Journal of Immunology. 195 (3): 973–981. PMID 26116501.
- Sánchez-Sánchez N, Riol-Blanco L, Rodríguez-Fernández JL (May 2006). "The multiple personalities of the chemokine receptor CCR7 in dendritic cells". Journal of Immunology. 176 (9): 5153–5159. PMID 16621978.
- Escribano C, Delgado-Martín C, Rodríguez-Fernández JL (November 2009). "CCR7-dependent stimulation of survival in dendritic cells involves inhibition of GSK3beta". Journal of Immunology. 183 (10): 6282–6295. PMID 19841191.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.