CXCL11 explained

C-X-C motif chemokine 11 (CXCL11) is a protein that in humans is encoded by the CXCL11 gene.^[1]

C-X-C motif chemokine 11 is a small cytokine belonging to the CXC chemokine family that is also called Interferon-inducible T-cell alpha chemoattractant (I-TAC) and Interferon-gamma-inducible protein 9 (IP-9). It is highly expressed in peripheral blood leukocytes, pancreas and liver, with moderate levels in thymus, spleen and lung and low expression levels were in small intestine, placenta and prostate.^[2]

Gene expression of CXCL11 is strongly induced by IFN-γ and IFN-β, and weakly induced by IFN-α.^[3] This chemokine elicits its effects on its target cells by interacting with the cell surface chemokine receptor CXCR3, with a higher affinity than do the other ligands for this receptor, CXCL9 and CXCL10.^{[2] [4]} CXCL11 is chemotactic for activated T cells. Its gene is located on human chromosome 4 along with many other members of the CXC chemokine family.^{[5] [6]}

Biomarkers

CXCL9, -10, -11 have proven to be valid biomarkers for the development of heart failure and left ventricular dysfunction, suggesting an underlining pathophysiological relation between levels of these chemokines and the development of adverse cardiac remodeling.^{[7] [8]}

Further reading

• Rani MR, Foster GR, Leung S, Leaman D, Stark GR, Ransohoff RM . Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha . The Journal of Biological Chemistry . 271 . 37 . 22878–84 . September 1996 . 8798467 . 10.1074/jbc.271.37.22878 . free .
• Jacobs KA, Collins-Racie LA, Colbert M, Duckett M, Golden-Fleet M, Kelleher K, Kriz R, LaVallie ER, Merberg D, Spaulding V, Stover J, Williamson MJ, McCoy JM . A genetic selection for isolating cDNAs encoding secreted proteins . Gene . 198 . 1–2 . 289–96 . October 1997 . 9370294 . 10.1016/S0378-1119(97)00330-2 .
• Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG, Neote K . Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3 . The Journal of Experimental Medicine . 187 . 12 . 2009–21 . June 1998 . 9625760 . 2212354 . 10.1084/jem.187.12.2009 .
• Erdel M, Laich A, Utermann G, Werner ER, Werner-Felmayer G . The human gene encoding SCYB9B, a putative novel CXC chemokine, maps to human chromosome 4q21 like the closely related genes for MIG (SCYB9) and INP10 (SCYB10) . Cytogenetics and Cell Genetics . 81 . 3–4 . 271–2 . 1998 . 9730616 . 10.1159/000015043 . 2024-07-29 . 46846304 .
• Luo Y, Kim R, Gabuzda D, Mi S, Collins-Racie LA, Lu Z, Jacobs KA, Dorf ME . The CXC-chemokine, H174: expression in the central nervous system . Journal of Neurovirology . 4 . 6 . 575–85 . December 1998 . 10065899 . 10.3109/13550289809114224 .
• Tensen CP, Flier J, Van Der Raaij-Helmer EM, Sampat-Sardjoepersad S, Van Der Schors RC, Leurs R, Scheper RJ, Boorsma DM, Willemze R . Human IP-9: A keratinocyte-derived high affinity CXC-chemokine ligand for the IP-10/Mig receptor (CXCR3) . The Journal of Investigative Dermatology . 112 . 5 . 716–22 . May 1999 . 10233762 . 10.1046/j.1523-1747.1999.00581.x . free .
• Laich A, Meyer M, Werner ER, Werner-Felmayer G . Structure and expression of the human small cytokine B subfamily member 11 (SCYB11/formerly SCYB9B, alias I-TAC) gene cloned from IFN-gamma-treated human monocytes (THP-1) . Journal of Interferon & Cytokine Research . 19 . 5 . 505–13 . May 1999 . 10386863 . 10.1089/107999099313956 .
• Tensen CP, Flier J, Rampersad SS, Sampat-Sardjoepersad S, Scheper RJ, Boorsma DM, Willemze R . Genomic organization, sequence and transcriptional regulation of the human CXCL 11(1) gene . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1446 . 1–2 . 167–72 . July 1999 . 10395932 . 10.1016/s0167-4781(99)00084-6 .
• Loetscher P, Pellegrino A, Gong JH, Mattioli I, Loetscher M, Bardi G, Baggiolini M, Clark-Lewis I . The ligands of CXC chemokine receptor 3, I-TAC, Mig, and IP10, are natural antagonists for CCR3 . The Journal of Biological Chemistry . 276 . 5 . 2986–91 . February 2001 . 11110785 . 10.1074/jbc.M005652200 . free .
• Lambeir AM, Proost P, Durinx C, Bal G, Senten K, Augustyns K, Scharpé S, Van Damme J, De Meester I . Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family . The Journal of Biological Chemistry . 276 . 32 . 29839–45 . August 2001 . 11390394 . 10.1074/jbc.M103106200 . free .
• Hensbergen PJ, van der Raaij-Helmer EM, Dijkman R, van der Schors RC, Werner-Felmayer G, Boorsma DM, Scheper RJ, Willemze R, Tensen CP . Processing of natural and recombinant CXCR3-targeting chemokines and implications for biological activity . European Journal of Biochemistry . 268 . 18 . 4992–9 . September 2001 . 11559369 . 10.1046/j.0014-2956.2001.02433.x .
• Mohan K, Ding Z, Hanly J, Issekutz TB . IFN-gamma-inducible T cell alpha chemoattractant is a potent stimulator of normal human blood T lymphocyte transendothelial migration: differential regulation by IFN-gamma and TNF-alpha . Journal of Immunology . 168 . 12 . 6420–8 . June 2002 . 12055261 . 10.4049/jimmunol.168.12.6420 . free .
• Basu S, Schaefer TM, Ghosh M, Fuller CL, Reinhart TA . Molecular cloning and sequencing of 25 different rhesus macaque chemokine cDNAs reveals evolutionary conservation among C, CC, CXC, AND CX3C families of chemokines . Cytokine . 18 . 3 . 140–8 . May 2002 . 12126650 . 10.1006/cyto.2002.0875 .
• Salmaggi A, Gelati M, Dufour A, Corsini E, Pagano S, Baccalini R, Ferrero E, Scabini S, Silei V, Ciusani E, De Rossi M . Expression and modulation of IFN-gamma-inducible chemokines (IP-10, Mig, and I-TAC) in human brain endothelium and astrocytes: possible relevance for the immune invasion of the central nervous system and the pathogenesis of multiple sclerosis . Journal of Interferon & Cytokine Research . 22 . 6 . 631–40 . June 2002 . 12162873 . 10.1089/10799900260100114 .
• Rani MR, Hibbert L, Sizemore N, Stark GR, Ransohoff RM . Requirement of phosphoinositide 3-kinase and Akt for interferon-beta-mediated induction of the beta-R1 (SCYB11) gene . The Journal of Biological Chemistry . 277 . 41 . 38456–61 . October 2002 . 12169689 . 10.1074/jbc.M203204200 . free .
• Kao J, Kobashigawa J, Fishbein MC, MacLellan WR, Burdick MD, Belperio JA, Strieter RM . Elevated serum levels of the CXCR3 chemokine ITAC are associated with the development of transplant coronary artery disease . Circulation . 107 . 15 . 1958–61 . April 2003 . 12695288 . 10.1161/01.CIR.0000069270.16498.75 . free .
• Satish L, Yager D, Wells A . Glu-Leu-Arg-negative CXC chemokine interferon gamma inducible protein-9 as a mediator of epidermal-dermal communication during wound repair . The Journal of Investigative Dermatology . 120 . 6 . 1110–7 . June 2003 . 12787142 . 10.1046/j.1523-1747.2003.12230.x . free .
• Klunker S, Trautmann A, Akdis M, Verhagen J, Schmid-Grendelmeier P, Blaser K, Akdis CA . A second step of chemotaxis after transendothelial migration: keratinocytes undergoing apoptosis release IFN-gamma-inducible protein 10, monokine induced by IFN-gamma, and IFN-gamma-inducible alpha-chemoattractant for T cell chemotaxis toward epidermis in atopic dermatitis . Journal of Immunology . 171 . 2 . 1078–84 . July 2003 . 12847282 . 10.4049/jimmunol.171.2.1078 . free .
• Xanthou G, Duchesnes CE, Williams TJ, Pease JE . CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 . European Journal of Immunology . 33 . 8 . 2241–50 . August 2003 . 12884299 . 10.1002/eji.200323787 . 24555816 .

Notes and References

1. Web site: Entrez Gene: CXCL11 chemokine (C-X-C motif) ligand 11.
2. Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG, Neote K . Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3 . The Journal of Experimental Medicine . 187 . 12 . 2009–21 . June 1998 . 9625760 . 2212354 . 10.1084/jem.187.12.2009 .
3. Rani MR, Foster GR, Leung S, Leaman D, Stark GR, Ransohoff RM . Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha . The Journal of Biological Chemistry . 271 . 37 . 22878–84 . September 1996 . 8798467 . 10.1074/jbc.271.37.22878 . free .
4. Tensen CP, Flier J, Van Der Raaij-Helmer EM, Sampat-Sardjoepersad S, Van Der Schors RC, Leurs R, Scheper RJ, Boorsma DM, Willemze R . Human IP-9: A keratinocyte-derived high affinity CXC-chemokine ligand for the IP-10/Mig receptor (CXCR3) . The Journal of Investigative Dermatology . 112 . 5 . 716–22 . May 1999 . 10233762 . 10.1046/j.1523-1747.1999.00581.x . free .
5. Erdel M, Laich A, Utermann G, Werner ER, Werner-Felmayer G . The human gene encoding SCYB9B, a putative novel CXC chemokine, maps to human chromosome 4q21 like the closely related genes for MIG (SCYB9) and INP10 (SCYB10) . Cytogenetics and Cell Genetics . 81 . 3–4 . 271–2 . 1998 . 9730616 . 10.1159/000015043 . 2024-07-29 . 46846304 .
6. O'Donovan N, Galvin M, Morgan JG . Physical mapping of the CXC chemokine locus on human chromosome 4 . Cytogenetics and Cell Genetics . 84 . 1–2 . 39–42 . 1999 . 10343098 . 10.1159/000015209 . 8087808 .
7. Altara R, Gu YM, Struijker-Boudier HA, Thijs L, Staessen JA, Blankesteijn WM . Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study . PLOS ONE . 10 . 10 . e0141394 . 2015 . 26506526 . 10.1371/journal.pone.0141394 . 4624781. 2015PLoSO..1041394A . free .
8. Altara R, Manca M, Hessel MH, Gu Y, van Vark LC, Akkerhuis KM, Staessen JA, Struijker-Boudier HA, Booz GW, Blankesteijn WM . CXCL10 Is a Circulating Inflammatory Marker in Patients with Advanced Heart Failure: a Pilot Study . Journal of Cardiovascular Translational Research . 9 . 4 . 302–14 . August 2016 . 27271043 . 10.1007/s12265-016-9703-3 . 41188765 .