CXCR3 Membrane Protein Introduction

Introduction of CXCR3

CXCR3 is a G protein-coupled receptor in the CXC chemokine receptor family, encoded by CXCR3 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. CXCR3 is widely expressed in many human tissues, such as lymph node, spleen. Recently, most studies focus on the role of CXCR3 in the pathological process of cancer.

Function of CXCR3 Membrane Protein

There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B, and chemokine receptor 3-alternative (CXCR3-alt). CXCR3-A is a receptor for CXCL9, CXCL10 and CXCL11. The binding of CXCR3-A and its ligands can regulate the proliferation, survival and angiogenic activity of human mesangial cell. CXCR3-B is a receptor for CXCL9, CXCL10, CXCL11 as well as CXCL4. Activated CXCR3-B can mediate the inhibition of proliferation, survival and angiogenic activity of human microvascular endothelial cells. Moreover, CXCR3 is widely expressed on activated T lymphocytes, NK cells, and some epithelial cells, involving in the regulation of inflammatory responses. In addition, some studies indicated that CXCR3 may play a role in the progression of multiple diseases, including atherosclerosis, autoimmune myasthenia gravis, nephrotoxic nephritis, type 1 diabetes, gastric cancer, liver cancer, breast cancer, hepatocellular carcinoma and so on. These also suggested that CXCR3 can be used as a therapeutic target for these diseases.

Fig.1 Chemokine receptor CXCR3 and its ligands CXCL9, CXCL10, and CXCL11. (Michlmayr, 2014)

Application of CXCR3 Membrane Protein in Literature

1. Chen F., et al. Expression of the chemokine receptor CXCR3 correlates with dendritic cell recruitment and prognosis in gastric cancer. Genetic Testing & Molecular Biomarkers. 2018, 22(1): 35-42. PubMed ID: 29266971
   
   

   The authors propose that higher CXCR3 expression in gastric cancer is associated with increased dendritic cells (DCs) and CD4⁺ and CD8⁺ tumor-infiltrating lymphocytes (TILs) infiltration as well as longer overall survival (OS). Thus the overexpression of CXCR3 may be a marker of favorable prognosis and a therapeutic target in gastric cancer.

2. Zhang Y., et al. CXCR3 is a prognostic marker and a potential target for patients with solid tumors: a meta-analysis. Oncotargets & Therapy. 2018, 11: 1045-1054. PubMed ID: 29520155
   
   

   The authors analyze the correlation between CXCR3 and patients’ prognosis based on 1,751 patients with solid tumors from 12 studies using a meta-analysis. Results show that the higher CXCR3 expression is significantly associated with shorter overall survival (OS) and distant metastasis in patients, suggesting that CXCR3 can act as a potential prognostic marker and a promising therapeutic target in solid tumors.

3. Weigold F., et al. Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive deterioration of lung function in patients with systemic sclerosis. Arthritis Research & Therapy. 2018, 20(1): 52. PubMed ID: 29566745
   
   

   The study indicates that anti-CXCR3/4 abs and their corresponding receptors are associated with the severity of SSc-ILD (systemic sclerosis-related interstitial lung disease). And antibody levels can be used to discriminate patients with stable or decreasing lung function.

4. Yin Z C., et al. Differential role of CXCR3 in inflammation and colorectal cancer. Eur Rev Med Pharmacol Sci. 2018, 22(8): 2454-2460. PubMed ID: 29762848
   
   

   CXCR3 is a kind of chemokine with the characteristic of recruiting inflammatory cells. This research aims to investigate the role of CXCR3 in cartilage injury. Results show that endoplasmic reticulum (ER) stress signaling pathway CHOP and GRP78 are involved in CXCR3 receptor attenuating chondrocyte apoptosis induced by sodium nitroprusside.

5. Gomaa A I., et al. The Role of Monocyte/Macrophage and CXCR3 in Differentiation between Recurrent Hepatitis C and Acute Cellular Rejection Postliver Transplantation. Journal of Immunology Research. 2018, 2018: 2726939. PubMed ID: 29854831
   
   

   The study suggests that the circulating blood-derived monocytes (BDM) and CXCR3 can help to differentiate between acute recurrent HCV and acute cellular rejection (ACR) after liver transplantation. CD11b (BDM marker) expression highlighting is in favor of recurrent hepatitis C and upregulation of CXCR3 is in favor of ACR.

CXCR3 Preparation Options

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Reference

1. Michlmayr D and Mckimmie CS. (2014). Role of CXCL10 in central nervous system inflammation. International Journal of Interferon Cytokine & Mediator Research. 2014(6), 1-18.

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