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Cxcr3  -  chemokine (C-X-C motif) receptor 3

Mus musculus

Synonyms: C-X-C chemokine receptor type 3, CXC-R3, CXCR-3, Cd183, Cmkar3, ...
 
 
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Disease relevance of Cxcr3

  • We examined the extent to which CXCR3 mediates resistance to dengue infection [1].
  • Remarkable differences in the cellular composition of the pulmonic granuloma of the CXCR3(-/-) and wild-type mice were found, the most striking being the increase in the number of CD4(+) T cells in the knockout strain [2].
  • Given the importance of Th1 immunity in the control of tuberculous infection, the results of the present study demonstrating that CXCR3-deficient BALB/c mice are more resistant to Mycobacterium tuberculosis, compared with wild-type mice, is surprising [2].
  • CXCR3-dependent recruitment of antigen-specific T lymphocytes to the liver during murine cytomegalovirus infection [3].
  • CXCR3 and its ligands participate in the host response to Bordetella bronchiseptica infection of the mouse respiratory tract but are not required for clearance of bacteria from the lung [4].
  • These findings indicate that the ameliorated nephritis in CXCR3-deficient mice is due to impaired renal trafficking of effector T cells rather than their inability to mount an efficient humoral or cellular immune response [5].
 

High impact information on Cxcr3

  • Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis [6].
  • Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs [7].
  • Molecular analyzes showed that the beneficial effects of targeting of LIGHT in CsA-treated recipients were accompanied by decreased intragraft expression of interferon (IFN)-gamma, plus IFN-gamma-induced chemokine, inducible protein-10, and its receptor, CXCR3 [8].
  • Expression of CXCR3, the receptor for MIG, was detected on a small subset of peripheral blood monocytes and on a significant percentage of recruited monocytes [9].
  • The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3 [10].
 

Chemical compound and disease context of Cxcr3

  • The Chemokine Receptor CXCR3 Attenuates the Control of Chronic Mycobacterium tuberculosis Infection in BALB/c Mice [2].
  • In this study, we investigated the therapeutic efficacy of a novel small-molecule compound, TAK779, an antagonist targeting both CCR5 and CXCR3 in intestinal ischemia/reperfusion (I/R) injury [11].
 

Biological context of Cxcr3

  • Interestingly, neutralization of CXCR3 or its ligands did not compromise host resistance to virus replication [12].
  • Furthermore, despite marked up-regulation of the two remaining CXCR3 ligands: CXCL9 and 11, we found a reduced accumulation of CD8(+) T cells in the brain parenchyma around the time point when wild-type mice succumb as a result of CD8(+) T cell-mediated inflammation [13].
  • The presence of cells bearing the chemokine receptors CCR5 and CXCR3, known to be preferentially expressed on Th1 and dendritic cells, was also synchronous with the kinetics of immune induction in the genital tract and clearance of infection [14].
  • We cloned the mouse homologue of the chemokine receptor CXCR3, which is located in mouse chromosome X. We screened a large panel of chemokines for their ability to induce a calcium flux in mouse CXCR3-transfected cells and identified a new ligand for this receptor, the recently reported CC chemokine 6Ckine [10].
  • We conclude that the CCL21-induced Cl(-) current is a prerequisite for the chemotaxis response mediated by the activation of CXCR3 but not CCR7 receptors, indicating that in brain CCL21 acts via a different receptor system than in lymphoid organs [15].
 

Anatomical context of Cxcr3

  • In the chronic phase of infection, the number of CD69-expressing CD4(+) T lymphocytes in the lungs of CXCR3(-/-) mice was higher than in wild-type mice [2].
  • Blockade of CXCR3 receptor:ligand interactions reduces leukocyte recruitment to the lung and the severity of experimental idiopathic pneumonia syndrome [16].
  • Additionally, at 1 mo postinfection, the number of IFN-gamma-producing CD4(+) T cells in the lungs and mediastinal lymph nodes of the CXCR3-deficient strain was elevated compared with wild-type mice [2].
  • We conclude that the CXCR3 receptor-ligand system contributes to pulmonary host defense in B. bronchiseptica infection by recruiting lymphocytes and NK cells into the lung [4].
  • However, the clearance of bacteria from the lung and trachea was delayed, and the recruitment of lymphocytes and NK cells was slightly decreased, for CXCR3(-/-) mice relative to CXCR3(+/+) mice [4].
 

Associations of Cxcr3 with chemical compounds

  • Estrogen treatment significantly decreased expression of proteins corresponding to the chemokine receptors CXCR3 and CCR5 on mammary cells [17].
  • TAK-779 is an antagonist for the chemokine receptors CCR5 and CXCR3, which are expressed on leukocytes, especially T-helper 1 cells, and these receptors may be involved in recruitment of these cells to atherosclerotic plaques [18].
  • CXCL10 was constitutively expressed by basal crypts in mouse colon, but the expression of CXCL10 as well as CXCR3 was enhanced in the epithelium in the proliferative zone after oral administration of dextran sulfate sodium [19].
  • METHODS: A/J strain murine islets were implanted to the kidney capsule of H-2 disparate, streptozotocin-induced diabetic wild type (WT), CXCR3 deficient (CXCR3(-/-)) or IP-10 antibody-treated WT (alphaIP-10) C57BL/6 recipients [20].
  • METHODS: Sex-, age-, and weight-matched C57BL/6 CXCR3 gene knockout mice and C57BL/6 wide type mice were challenged by injection of bleomycin via trachea [21].
 

Regulatory relationships of Cxcr3

  • However, analysis of the susceptibility of CXCL10-deficient mice to lymphocytic choriomeningitis virus-induced meningitis revealed that these mice just like CXCR3-deficient mice were partially resistant to this disease, whereas wild-type mice invariably died [13].
  • Reconstitution of these mice with IFN-gamma induced CXCR3 ligand synthesis [22].
  • In line with this, CXCR3 is expressed preferentially in Th1 cells and in lymphoid organs of the IL-10(-/-) mouse that develops chronic colitis [10].
  • In contrast, CXCR3 was induced on STAT4-deficient T cells independently of IL-12 stimulation as long as IFN-gamma was produced as a result of potent TCR stimulation [23].
 

Other interactions of Cxcr3

 

Analytical, diagnostic and therapeutic context of Cxcr3

References

  1. Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. Hsieh, M.F., Lai, S.L., Chen, J.P., Sung, J.M., Lin, Y.L., Wu-Hsieh, B.A., Gerard, C., Luster, A., Liao, F. J. Immunol. (2006) [Pubmed]
  2. The Chemokine Receptor CXCR3 Attenuates the Control of Chronic Mycobacterium tuberculosis Infection in BALB/c Mice. Chakravarty, S.D., Xu, J., Lu, B., Gerard, C., Flynn, J., Chan, J. J. Immunol. (2007) [Pubmed]
  3. CXCR3-dependent recruitment of antigen-specific T lymphocytes to the liver during murine cytomegalovirus infection. Hokeness, K.L., Deweerd, E.S., Munks, M.W., Lewis, C.A., Gladue, R.P., Salazar-Mather, T.P. J. Virol. (2007) [Pubmed]
  4. CXCR3 and its ligands participate in the host response to Bordetella bronchiseptica infection of the mouse respiratory tract but are not required for clearance of bacteria from the lung. Widney, D.P., Hu, Y., Foreman-Wykert, A.K., Bui, K.C., Nguyen, T.T., Lu, B., Gerard, C., Miller, J.F., Smith, J.B. Infect. Immun. (2005) [Pubmed]
  5. Chemokine receptor CXCR3 mediates T cell recruitment and tissue injury in nephrotoxic nephritis in mice. Panzer, U., Steinmetz, O.M., Paust, H.J., Meyer-Schwesinger, C., Peters, A., Turner, J.E., Zahner, G., Heymann, F., Kurts, C., Hopfer, H., Helmchen, U., Haag, F., Schneider, A., Stahl, R.A. J. Am. Soc. Nephrol. (2007) [Pubmed]
  6. Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis. Frigerio, S., Junt, T., Lu, B., Gerard, C., Zumsteg, U., Holländer, G.A., Piali, L. Nat. Med. (2002) [Pubmed]
  7. Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Martín-Fontecha, A., Thomsen, L.L., Brett, S., Gerard, C., Lipp, M., Lanzavecchia, A., Sallusto, F. Nat. Immunol. (2004) [Pubmed]
  8. Modulation of LIGHT-HVEM costimulation prolongs cardiac allograft survival. Ye, Q., Fraser, C.C., Gao, W., Wang, L., Busfield, S.J., Wang, C., Qiu, Y., Coyle, A.J., Gutierrez-Ramos, J.C., Hancock, W.W. J. Exp. Med. (2002) [Pubmed]
  9. Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment. Janatpour, M.J., Hudak, S., Sathe, M., Sedgwick, J.D., McEvoy, L.M. J. Exp. Med. (2001) [Pubmed]
  10. The CC chemokine 6Ckine binds the CXC chemokine receptor CXCR3. Soto, H., Wang, W., Strieter, R.M., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Hedrick, J., Zlotnik, A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. A Novel CCR5/CXCR3 Antagonist Protects Intestinal Ischemia/Reperfusion Injury. Akahori, T., Sho, M., Kashizuka, H., Nomi, T., Kanehiro, H., Nakajima, Y. Transplant. Proc. (2006) [Pubmed]
  12. CXCR3, IP-10, and Mig are required for CD4+ T cell recruitment during the DTH response to HSV-1 yet are independent of the mechanism for viral clearance. Molesworth-Kenyon, S., Mates, A., Yin, R., Strieter, R., Oakes, J., Lausch, R. Virology (2005) [Pubmed]
  13. CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system. Christensen, J.E., de Lemos, C., Moos, T., Christensen, J.P., Thomsen, A.R. J. Immunol. (2006) [Pubmed]
  14. Chemokine and chemokine receptor dynamics during genital chlamydial infection. Belay, T., Eko, F.O., Ananaba, G.A., Bowers, S., Moore, T., Lyn, D., Igietseme, J.U. Infect. Immun. (2002) [Pubmed]
  15. Secondary lymphoid tissue chemokine (CCL21) activates CXCR3 to trigger a Cl- current and chemotaxis in murine microglia. Rappert, A., Biber, K., Nolte, C., Lipp, M., Schubel, A., Lu, B., Gerard, N.P., Gerard, C., Boddeke, H.W., Kettenmann, H. J. Immunol. (2002) [Pubmed]
  16. Blockade of CXCR3 receptor:ligand interactions reduces leukocyte recruitment to the lung and the severity of experimental idiopathic pneumonia syndrome. Hildebrandt, G.C., Corrion, L.A., Olkiewicz, K.M., Lu, B., Lowler, K., Duffner, U.A., Moore, B.B., Kuziel, W.A., Liu, C., Cooke, K.R. J. Immunol. (2004) [Pubmed]
  17. Estrogen disrupts chemokine-mediated chemokine release from mammary cells: implications for the interplay between estrogen and IP-10 in the regulation of mammary tumor formation. Aronica, S.M., Fanti, P., Kaminskaya, K., Gibbs, K., Raiber, L., Nazareth, M., Bucelli, R., Mineo, M., Grzybek, K., Kumin, M., Poppenberg, K., Schwach, C., Janis, K. Breast Cancer Res. Treat. (2004) [Pubmed]
  18. HIV entry inhibitor TAK-779 attenuates atherogenesis in low-density lipoprotein receptor-deficient mice. van Wanrooij, E.J., Happé, H., Hauer, A.D., de Vos, P., Imanishi, T., Fujiwara, H., van Berkel, T.J., Kuiper, J. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  19. Blockade of CXCL10 protects mice from acute colitis and enhances crypt cell survival. Sasaki, S., Yoneyama, H., Suzuki, K., Suriki, H., Aiba, T., Watanabe, S., Kawauchi, Y., Kawachi, H., Shimizu, F., Matsushima, K., Asakura, H., Narumi, S. Eur. J. Immunol. (2002) [Pubmed]
  20. Genetic deletion of chemokine receptor CXCR3 or antibody blockade of its ligand IP-10 modulates posttransplantation graft-site lymphocytic infiltrates and prolongs functional graft survival in pancreatic islet allograft recipients. Baker, M.S., Chen, X., Rotramel, A.R., Nelson, J.J., Lu, B., Gerard, C., Kanwar, Y., Kaufman, D.B. Surgery (2003) [Pubmed]
  21. CXC chemokine receptor 3 modulates bleomycin-induced pulmonary injury via involving inflammatory process. Gao, J.M., Lu, B., Guo, Z.J. Chin. Med. Sci. J. (2006) [Pubmed]
  22. A novel role for neutrophils as a source of T cell-recruiting chemokines IP-10 and Mig during the DTH response to HSV-1 antigen. Molesworth-Kenyon, S.J., Oakes, J.E., Lausch, R.N. J. Leukoc. Biol. (2005) [Pubmed]
  23. Induction of the chemokine receptor CXCR3 on TCR-stimulated T cells: dependence on the release from persistent TCR-triggering and requirement for IFN-gamma stimulation. Nakajima, C., Mukai, T., Yamaguchi, N., Morimoto, Y., Park, W.R., Iwasaki, M., Gao, P., Ono, S., Fujiwara, H., Hamaoka, T. Eur. J. Immunol. (2002) [Pubmed]
  24. Peptide nucleic acid antisense prolongs skin allograft survival by means of blockade of CXCR3 expression directing T cells into graft. Jiankuo, M., Xingbing, W., Baojun, H., Xiongwin, W., Zhuoya, L., Ping, X., Yong, X., Anting, L., Chunsong, H., Feili, G., Jinquan, T. J. Immunol. (2003) [Pubmed]
  25. Estrogen decreases expression of chemokine receptors, and suppresses chemokine bioactivity in murine monocytes. Janis, K., Hoeltke, J., Nazareth, M., Fanti, P., Poppenberg, K., Aronica, S.M. Am. J. Reprod. Immunol. (2004) [Pubmed]
  26. Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice. Wareing, M.D., Lyon, A.B., Lu, B., Gerard, C., Sarawar, S.R. J. Leukoc. Biol. (2004) [Pubmed]
  27. Chemokine and chemokine receptor expression during experimental autoimmune uveoretinitis in mice. Keino, H., Takeuchi, M., Kezuka, T., Yamakawa, N., Tsukahara, R., Usui, M. Graefes Arch. Clin. Exp. Ophthalmol. (2003) [Pubmed]
 
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