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CXCR5

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CXCR5
Identifiers
AliasesCXCR5, BLR1, CD185, MDR15, C-X-C motif chemokine receptor 5, C-X-C chemokine receptor type 5
External IDsOMIM: 601613; MGI: 103567; HomoloGene: 1298; GeneCards: CXCR5; OMA:CXCR5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

643

12145

Ensembl

ENSG00000160683

ENSMUSG00000047880

UniProt

P32302

Q04683

RefSeq (mRNA)

NM_032966
NM_001716

NM_007551

RefSeq (protein)

NP_001707
NP_116743

NP_031577

Location (UCSC)Chr 11: 118.88 – 118.9 MbChr 9: 44.42 – 44.47 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

C-X-C chemokine receptor type 5 (CXC-R5) also known as CD185 (cluster of differentiation 185) or Burkitt lymphoma receptor 1 (BLR1) is a G protein-coupled seven transmembrane receptor for chemokine CXCL13 (also known as BLC) and belongs to the CXC chemokine receptor family. It enables T cells to migrate to lymph node and the B cell zones. In humans, the CXC-R5 protein is encoded by the CXCR5 gene.[5]

Tissue distribution and function

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The BLR1 / CXCR5 gene is specifically expressed in Burkitt's lymphoma and lymphatic tissues, such as follicles in lymph nodes as well as in spleen. The gene plays an essential role in B cell migration.[6] Through CXCL13 secretions B cells are able to locate the lymph node.[6]

Additionally, some recent studies have suggested that CXCL13, through CXCR5, is capable of recruiting hematopoietic precursor cells (CD3− CD4+) which would cause the development of lymph nodes and Peyer's Patches.[7][8]

Other studies highlight the role of CXCR5 in T cells, as they are unable to access B cell follicles without CXCR5 expression.[9][10] This is a key step in the production of high affinity antibodies as B cells and T cells need to interact in order to activate the Ig class switch.[9]

CXCR5 has been shown to be expressed on both CD4[11] and CD8[12] T cells, though it is often regarded as the defining marker for T Follicular Helper (Tfh) cells.[13]

Role in cancer development

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Recently, it was shown that CXCR5 overexpression in breast cancer patients highly correlates with lymph node metastases,[14] and elevated CXCR5 expression may contribute to abnormal cell survival and migration in breast tumors that lack functional p53 protein.[15] Minor allele of SNP rs630923, located in the area of CXCR5 gene promoter and associated with the risk of multiple sclerosis, is responsible for appearance of MEF2C-binding site resulted in reduced CXCR5 gene promoter activity in B-cells during activation, that could lead to decreased autoimmune response [16]

While chemokines and chemokine receptors have been thought to be involved in cancer development and maintenance, recently CXCR5 has come under investigation for its role in metastatic progression of prostate cancer. A recent study has indicated that prostate cancer tissue as well as cell lines express higher non-basal levels of CXCR5.[17] Furthermore, the study found a correlation between the level of CXCR5 and Gleason score. CXCR5 location was additionally considered and higher Gleason scores correlated with nuclear CXCR5 while cytoplasmic and membrane CXCR5 correlated with benign and early prostate cancers.[17]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000160683 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000047880 – 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. ^ Dobner T, Wolf I, Emrich T, Lipp M (November 1992). "Differentiation-specific expression of a novel G protein-coupled receptor from Burkitt's lymphoma". European Journal of Immunology. 22 (11): 2795–2799. doi:10.1002/eji.1830221107. PMID 1425907. S2CID 35096818.
  6. ^ a b Förster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M (December 1996). "A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen". Cell. 87 (6): 1037–1047. doi:10.1016/S0092-8674(00)81798-5. PMID 8978608. S2CID 17558174.
  7. ^ Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P, Ikuta K, et al. (March 2001). "Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis". The Journal of Experimental Medicine. 193 (5): 621–630. doi:10.1084/jem.193.5.621. PMC 2193398. PMID 11238592.
  8. ^ Finke D, Acha-Orbea H, Mattis A, Lipp M, Kraehenbuhl J (September 2002). "CD4+CD3- cells induce Peyer's patch development: role of alpha4beta1 integrin activation by CXCR5". Immunity. 17 (3): 363–373. doi:10.1016/S1074-7613(02)00395-3. PMID 12354388.
  9. ^ a b Junt T, Fink K, Förster R, Senn B, Lipp M, Muramatsu M, et al. (December 2005). "CXCR5-dependent seeding of follicular niches by B and Th cells augments antiviral B cell responses". Journal of Immunology. 175 (11): 7109–7116. doi:10.4049/jimmunol.175.11.7109. PMID 16301613.
  10. ^ Hardtke S, Ohl L, Förster R (September 2005). "Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help". Blood. 106 (6): 1924–1931. doi:10.1182/blood-2004-11-4494. PMID 15899919.
  11. ^ Chevalier N, Jarrossay D, Ho E, Avery DT, Ma CS, Yu D, et al. (May 2011). "CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses". Journal of Immunology. 186 (10): 5556–5568. doi:10.4049/jimmunol.1002828. PMID 21471443.
  12. ^ He R, Hou S, Liu C, Zhang A, Bai Q, Han M, et al. (August 2016). "Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection". Nature. 537 (7620): 412–428. Bibcode:2016Natur.537..412H. doi:10.1038/nature19317. PMID 27501245. S2CID 4469688.
  13. ^ Moser B (2015). "CXCR5, the Defining Marker for Follicular B Helper T (TFH) Cells". Frontiers in Immunology. 6: 296. doi:10.3389/fimmu.2015.00296. PMC 4459225. PMID 26106395.
  14. ^ Biswas S, Sengupta S, Roy Chowdhury S, Jana S, Mandal G, Mandal PK, et al. (January 2014). "CXCL13-CXCR5 co-expression regulates epithelial to mesenchymal transition of breast cancer cells during lymph node metastasis". Breast Cancer Research and Treatment. 143 (2): 265–276. doi:10.1007/s10549-013-2811-8. PMID 24337540. S2CID 2937341.
  15. ^ Mitkin NA, Hook CD, Schwartz AM, Biswas S, Kochetkov DV, Muratova AM, et al. (March 2015). "p53-dependent expression of CXCR5 chemokine receptor in MCF-7 breast cancer cells". Scientific Reports. 5 (5): 9330. Bibcode:2015NatSR...5E9330M. doi:10.1038/srep09330. PMC 4365401. PMID 25786345.
  16. ^ Mitkin NA, Muratova AM, Schwartz AM, Kuprash DV (Nov 2016). "The A Allele of the Single-Nucleotide Polymorphism rs630923 Creates a Binding Site for MEF2C Resulting in Reduced CXCR5 Promoter Activity in B-Cell Lymphoblastic Cell Lines". Frontiers in Immunology. 7 (515): 515. doi:10.3389/fimmu.2016.00515. PMC 5112242. PMID 27909439.
  17. ^ a b Singh S, Singh R, Singh UP, Rai SN, Novakovic KR, Chung LW, et al. (November 2009). "Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines". International Journal of Cancer. 125 (10): 2288–2295. doi:10.1002/ijc.24574. PMC 3600527. PMID 19610059.

Further reading

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