CXCR5

Last updated
CXCR5
Identifiers
Aliases CXCR5 , BLR1, CD185, MDR15, C-X-C motif chemokine receptor 5, C-X-C chemokine receptor type 5
External IDs OMIM: 601613 MGI: 103567 HomoloGene: 1298 GeneCards: CXCR5
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 Mb Chr 9: 44.42 – 44.47 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

Tissue distribution and function

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

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]

Related Research Articles

<span class="mw-page-title-main">Stromal cell-derived factor 1</span> Mammalian protein found in Homo sapiens

The stromal cell-derived factor 1 (SDF-1), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein that in humans is encoded by the CXCL12 gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types. Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the chemokine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1. The chemokines are characterized by the presence of 4 conserved cysteines that form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, the cysteine residues are adjacent to each other. In the CXC subfamily, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group. CXCL12 signaling has been observed in several cancers. The CXCL12 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">Chemokine</span> Small cytokines or signaling proteins secreted by cells

Chemokines, or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.

<span class="mw-page-title-main">CXCR4</span> Protein

C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene. The protein is a CXC chemokine receptor.

<span class="mw-page-title-main">Follicular dendritic cells</span> Immune cells found in lymph nodes

Follicular dendritic cells (FDC) are cells of the immune system found in primary and secondary lymph follicles of the B cell areas of the lymphoid tissue. Unlike dendritic cells (DC), FDCs are not derived from the bone-marrow hematopoietic stem cell, but are of mesenchymal origin. Possible functions of FDC include: organizing lymphoid tissue's cells and microarchitecture, capturing antigen to support B cell, promoting debris removal from germinal centers, and protecting against autoimmunity. Disease processes that FDC may contribute include primary FDC-tumor, chronic inflammatory conditions, HIV-1 infection development, and neuroinvasive scrapie.

<span class="mw-page-title-main">CCL21</span> Mammalian protein found in Homo sapiens

Chemokine ligand 21 (CCL21) is a small cytokine belonging to the CC chemokine family. This chemokine is also known as 6Ckine, exodus-2, and secondary lymphoid-tissue chemokine (SLC). CCL21 elicits its effects by binding to a cell surface chemokine receptor known as CCR7. The main function of CCL21 is to guide CCR7 expressing leukocytes to the secondary lymphoid organs, such as lymph nodes and Peyer´s patches.

<span class="mw-page-title-main">CXCL9</span> Mammalian protein found in Homo sapiens

Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.

<span class="mw-page-title-main">CXCL11</span> Mammalian protein found in Homo sapiens

C-X-C motif chemokine 11 (CXCL11) is a protein that in humans is encoded by the CXCL11 gene.

<span class="mw-page-title-main">CXCL1</span> Mammalian protein found in Homo sapiens

The chemokine ligand 1 (CXCL1) is a small peptide belonging to the CXC chemokine family that acts as a chemoattractant for several immune cells, especially neutrophils or other non-hematopoietic cells to the site of injury or infection and plays an important role in regulation of immune and inflammatory responses. It was previously called GRO1 oncogene, GROα, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). CXCL1 was first cloned from a cDNA library of genes induced by platelet-derived growth factor (PDGF) stimulation of BALB/c-3T3 murine embryonic fibroblasts and named "KC" for its location in the nitrocellulose colony hybridization assay. This designation is sometimes erroneously believed to be an acronym and defined as "keratinocytes-derived chemokine". Rat CXCL1 was first reported when NRK-52E cells were stimulated with interleukin-1β (IL-1β) and lipopolysaccharide (LPS) to generate a cytokine that was chemotactic for rat neutrophils, cytokine-induced neutrophil chemoattractant (CINC). In humans, this protein is encoded by the gene Cxcl1 and is located on human chromosome 4 among genes for other CXC chemokines.

<span class="mw-page-title-main">CXCL2</span> Mammalian protein found in Homo sapiens

Chemokine ligand 2 (CXCL2) is a small cytokine belonging to the CXC chemokine family that is also called macrophage inflammatory protein 2-alpha (MIP2-alpha), Growth-regulated protein beta (Gro-beta) and Gro oncogene-2 (Gro-2). CXCL2 is 90% identical in amino acid sequence as a related chemokine, CXCL1. This chemokine is secreted by monocytes and macrophages and is chemotactic for polymorphonuclear leukocytes and hematopoietic stem cells. The gene for CXCL2 is located on human chromosome 4 in a cluster of other CXC chemokines. CXCL2 mobilizes cells by interacting with a cell surface chemokine receptor called CXCR2.

<span class="mw-page-title-main">CXCL5</span> Mammalian protein found in Homo sapiens

C-X-C motif chemokine 5 is a protein that in humans is encoded by the CXCL5 gene.

<span class="mw-page-title-main">CXCL13</span> Mammalian protein found in Homo sapiens

Chemokine ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1), is a protein ligand that in humans is encoded by the CXCL13 gene.

CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins, since they span the cell membrane seven times. There are currently six known CXC chemokine receptors in mammals, named CXCR1 through CXCR6.

Chemokine ligand 17 (CXCL17) is a small cytokine belonging to the CXC chemokine family that has been identified in humans and mice. CXCL17 attracts dendritic cells and monocytes and is regulated in tumors. It is also known as VEGF co-regulated chemokine 1 (VCC-1) and dendritic cell- and monocyte-attracting chemokine-like protein (DMC). This chemokine is constitutively expressed in the lung. The gene for human CXCL17 is located on chromosome 19.

<span class="mw-page-title-main">CXCR3</span> Protein-coding gene in humans

Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B and chemokine receptor 3-alternative (CXCR3-alt). CXCR3-A binds to the CXC chemokines CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC) whereas CXCR3-B can also bind to CXCL4 in addition to CXCL9, CXCL10, and CXCL11.

<span class="mw-page-title-main">Interleukin 8 receptor, beta</span> Mammalian protein found in Homo sapiens

Interleukin 8 receptor, beta is a chemokine receptor. IL8RB is also known as CXCR2, and CXCR2 is now the IUPHAR Committee on Receptor Nomenclature and Drug classification-recommended name.

<span class="mw-page-title-main">C-C chemokine receptor type 7</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for this receptor: the chemokines ligand 19 (CCL19/ELC) and ligand 21 (CCL21). 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. 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 by detecting specific chemokines, which these tissues secrete.

<span class="mw-page-title-main">GPR183</span> Protein-coding gene in the species Homo sapiens

G-protein coupled receptor 183 also known as Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) is a protein (GPCR) expressed on the surface of some immune cells, namely B cells and T cells; in humans it is encoded by the GPR183 gene. Expression of EBI2 is one critical mediator of immune cell localization within lymph nodes, responsible in part for the coordination of B cell, T cell, and dendritic cell movement and interaction following antigen exposure. EBI2 is a receptor for oxysterols. The most potent activator is 7α,25-dihydroxycholesterol (7α,25-OHC), with other oxysterols exhibiting varying affinities for the receptor. Oxysterol gradients drive chemotaxis, attracting the EBI2-expressing cells to locations of high ligand concentration. The GPR183 gene was identified due to its upregulation during Epstein-Barr virus infection of the Burkitt's lymphoma cell line BL41, hence its name: EBI2.

<span class="mw-page-title-main">ACKR3</span> Mammalian protein found in Homo sapiens

Atypical chemokine receptor 3 also known as C-X-C chemokine receptor type 7 (CXCR-7) and G-protein coupled receptor 159 (GPR159) is a protein that in humans is encoded by the ACKR3 gene.

<span class="mw-page-title-main">CXCR6</span>

C-X-C chemokine receptor type 6 is a protein that in humans is encoded by the CXCR6 gene. CXCR6 has also recently been designated CD186.

Lymph node stromal cells are essential to the structure and function of the lymph node whose functions include: creating an internal tissue scaffold for the support of hematopoietic cells; the release of small molecule chemical messengers that facilitate interactions between hematopoietic cells; the facilitation of the migration of hematopoietic cells; the presentation of antigens to immune cells at the initiation of the adaptive immune system; and the homeostasis of lymphocyte numbers. Stromal cells originate from multipotent mesenchymal stem cells.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000160683 - Ensembl, May 2017
  2. 1 2 3 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): 2795–9. doi:10.1002/eji.1830221107. PMID   1425907. S2CID   35096818.
  6. 1 2 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): 1037–47. doi: 10.1016/S0092-8674(00)81798-5 . PMID   8978608. S2CID   17558174.
  7. ↑ Honda, Kenya; Nakano, Hiroyasu; Yoshida, Hisahiro; Nishikawa, Satomi; Rennert, Paul; Ikuta, Koichi; Tamechika, Masakatsu; Yamaguchi, Kazuhito; Fukumoto, Tetsuo (2001-03-05). "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. ISSN   0022-1007. PMC   2193398 . PMID   11238592.
  8. ↑ Finke, D; Acha-Orbea, H; Mattis, A; Lipp, M; Kraehenbuhl, J.P (September 2002). "CD4+CD3− Cells Induce Peyer's Patch Development". Immunity. 17 (3): 363–373. doi: 10.1016/S1074-7613(02)00395-3 . PMID   12354388.
  9. 1 2 Junt, Tobias; Fink, Katja; Förster, Reinhold; Senn, Beatrice; Lipp, Martin; Muramatsu, Masamichi; Zinkernagel, Rolf M.; Ludewig, Burkhard; Hengartner, Hans (2005-12-01). "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 . ISSN   0022-1767. PMID   16301613.
  10. ↑ Hardtke, S. (2005-09-15). "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 . ISSN   0006-4971. PMID   15899919.
  11. ↑ Chevalier N, Jarrossay D, Ho E, Avery DT, Ma CS, Yu D, Sallusto F, Tangye SG, Mackay CR (May 2011). "CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses". Journal of Immunology. 186 (10): 5556–68. doi: 10.4049/jimmunol.1002828 . PMID   21471443.
  12. ↑ He R, Hou S, Liu C, Zhang A, Bai Q, Han M, Yang Y, Wei G, Shen T, Yang X, Xu L, Chen X, Hao Y, Wang P, Zhu C, Ou J, Liang H, Ni T, Zhang X, Zhou X, Deng K, Chen Y, Luo Y, Xu J, Qi H, Wu Y, Ye L (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, Saha N, Malhotra V, Gupta A, Kuprash DV, Bhattacharyya A (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): 265–76. doi:10.1007/s10549-013-2811-8. PMID   24337540. S2CID   2937341.
  15. ↑ Mitkin NA, Hook CD, Schwartz AM, Biswas S, Kochetkov DV, Muratova AM, Afanasyeva MA, Kravchenko JE, Bhattacharyya A, Kuprash DV (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. 1 2 Singh, Shailesh; Singh, Rajesh; Singh, Udai P.; Rai, Shesh N.; Novakovic, Kristian R.; Chung, Leland W.K.; Didier, Peter J.; Grizzle, William E.; Lillard, James W. (2009-11-15). "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.

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