CXCR5 Membrane Protein Introduction

Introduction of CXCR5

CXCR5 is a G protein-coupled receptor in the CXC chemokine receptor family, encoded by CXCR5 gene. It is one of seven CXC chemokine receptors (CXCR1-CXCR7) in mammals. The receptors can recognize CXC chemokine that possesses an E-L-R amino acid motif. CXCR5 is specifically expressed in mature B-cell and Burkitt's lymphoma. Recently, most studies focus on the role of CXCR5 in the pathological process of cancer.

Function of CXCR5 Membrane Protein

CXCR5 can bind to B-lymphocyte chemoattractant (BLC), also known as CXCL13, and is involved in B-cell migration into B-cell follicles of spleen and Peyer patches. CXCL13/CXCR5 plays an essential role in the progression of multiple diseases. In neurosyphilis patients, CXCL13/CXCR5 mediates the aggregation of B cells, resulting in ectopic germinal centers (EGCs) formation in the intracranial syphilitic gumma, inducing the abnormal humoral immune response. Besides, the expression of CXCR5 is associated with the pathogenesis of multiple tumors, such as colorectal cancer, breast cancer, prostate cancer, and chronic lymphocytic leukemia. The elevated CXCR5 expression may be observed in breast tumors that may contribute to abnormal cell survival and migration. Similarly, the expression of CXCR5 can promote the pathogenesis, development, metastasis, and relapse of colorectal cancer. It also suggests that blockade of CXCR5 may serve as an effective therapy for tumors. Recently, more and more studies focus on the role of CXCR5 in the pathological process of cancer, expecting to obtain a new therapeutic strategy for cancer.

Fig. 1 Reciprocal cross-talk between CLL cells and FDCs in the germinal center. (Lopezguerra, 2014)

Application of CXCR5 Membrane Protein in Literature

1. Xu L., et al. Signaling via the CXCR5/ERK pathway is mediated by CXCL13 in mice with breast cancer. Oncology Letters. 2018, 15(6): 9293-9298. PubMed ID: 29844827
   
   

   The research suggests that CXCL13 inhibitor reduce the volume and growth of tumor as well as the mRNA and protein expression levels of key members (CXCL13, CXCR5, and ERK) of the CXCR5/ERK signaling pathway. So authors propose the recession of tumors induced by CXCL13 inhibitor may be associated with the CXCR5/ERK signaling pathway.

2. Zhang X., et al. CXCR5-overexpressing mesenchymal stromal cells exhibit enhanced homing and can decrease contact hypersensitivity. Molecular Therapy. 2017, 25(6): 1434-1447. PubMed ID: 28454789
   
   

   The study shows that the overexpression of CXCR5 increases the ability of mesenchymal stromal cells (MSCs) to respond to migratory stimuli and highly intensifies their immunomodulatory effects in vivo. This strategy for enhancing targeted stem/progenitor cell homing may improve the efficacy of MSC-based therapies.

3. Zhang D., et al. miR-192 suppresses T follicular helper cell differentiation by targeting CXCR5 in childhood asthma. Scand J Clin Lab Invest. 2018, 78(3): 236-242. PubMed ID: 29490514
   
   

   The research aims to investigate the role of miR-192 in the differentiation of T follicular helper cells in childhood asthma. Results show that miR-192 blocks the activation pathway of Tfh cells by targeting CXCR5, which is a reasonable cellular target for therapeutic intervention.

4. Aqrawi L A., et al. Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing. Clinical & Experimental Immunology. 2018, 192(3): 259-270. PubMed ID: 29453859
   
   

   The study shows that a susceptible allele for Sjögren's syndrome (SS) is linked with decreased CXCR5 expression. And the decrease of CXCR5⁺ cells in circulation is also related to homing of B and T cells to the autoimmune target organ. These suggest that CXCR5/CXCL13 axis may be a useful therapeutic drugs target for SS.

5. Mitkin N A., et al. P63 and p73 repress CXCR5 chemokine receptor gene expression in p53-deficient MCF-7 breast cancer cells during genotoxic stress. Biochimica Et Biophysica Acta. 2017, 1860(12): 1169-1178. PubMed ID: 29107083
   
   

   The study identifies that the effects of NFkB on the CXCR5 promoter inversely correlated with p63 and p73 levels via deletion analysis and site-directed mutagenesis. Thus all three p53 family members are involved in the mediation of the effects of genotoxic stress on the CXCR5 promoter using the same mechanism associated with attenuation of NFkB activity.

CXCR5 Preparation Options

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Reference

1. Lopezguerra M, et al. (2014). CXCR5-mediated shaping of the lymphoid follicle in chronic lymphocytic leukemia. Cancer Discovery. 4(12), 1374-76.

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