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Chemokine (C-X-C motif) ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as Monokine induced by gamma interferon (MIG). CXCL9 is a T-cell chemoattractant, which is induced by IFN-γ. It is closely related to two other CXC chemokines called CXCL10 and CXCL11, whose genes are located near the gene for CXCL9 on human chromosome 4.[1][2] CXCL9, CXCL10 and CXCL11 all elicit their chemotactic functions by interacting with the chemokine receptor CXCR3.[3]

Neutrophil collagenase/matrix metalloproteinase 8 (MMP-8) degrades CXCL9 and cleaves CXCL10 at two positions.

Gelatinase B/matrix metalloproteinase 9 (MMP-9) degrades CXCL10 and cleaves CXCL9 at three different sites in its extended carboxy-terminal region.


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.[4][5]

This chemokine has also been associated as a biomarker for diagnosing Q fever infections.[6]


CXCL9 has been shown to interact with CXCR3.[7][8]


  1. Lee HH, Farber JM (1996). "Localization of the gene for the human MIG cytokine on chromosome 4q21 adjacent to INP10 reveals a chemokine "mini-cluster"". Cytogenetics and Cell Genetics. 74 (4): 255–8. doi:10.1159/000134428. PMID 8976378.
  2. O'Donovan N, Galvin M, Morgan JG (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenetics and Cell Genetics. 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098.
  3. Tensen CP, Flier J, Van Der Raaij-Helmer EM, Sampat-Sardjoepersad S, Van Der Schors RC, Leurs R, Scheper RJ, Boorsma DM, Willemze R (May 1999). "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. doi:10.1046/j.1523-1747.1999.00581.x. PMID 10233762.
  4. Altara R, Gu YM, Struijker-Boudier HA, Thijs L, Staessen JA, Blankesteijn WM (2015). "Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study". PLOS ONE. 10 (10): e0141394. doi:10.1371/journal.pone.0141394. PMC 4624781. PMID 26506526.
  5. Altara R, Manca M, Hessel MH, Gu Y, van Vark LC, Akkerhuis KM, Staessen JA, Struijker-Boudier HA, Booz GW, Blankesteijn WM (August 2016). "CXCL10 Is a Circulating Inflammatory Marker in Patients with Advanced Heart Failure: a Pilot Study". Journal of Cardiovascular Translational Research. 9 (4): 302–14. doi:10.1007/s12265-016-9703-3. PMID 27271043.
  6. Jansen AFM, Schoffelen T, Textoris J, Mege JL, Nabuurs-Franssen M, Raijmakers RPH, Netea MG, Joosten LAB, Bleeker-Rovers CP, van Deuren M (2017). "CXCL9, a promising biomarker in the diagnosis of chronic Q fever". BMC Infect. Dis. 17 (1): 556. doi:10.1186/s12879-017-2656-6. PMC 5551022. PMID 28793883.
  7. Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (June 2003). "An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4". The Journal of Experimental Medicine. 197 (11): 1537–49. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716.
  8. Weng Y, Siciliano SJ, Waldburger KE, Sirotina-Meisher A, Staruch MJ, Daugherty BL, Gould SL, Springer MS, DeMartino JA (July 1998). "Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors". The Journal of Biological Chemistry. 273 (29): 18288–91. doi:10.1074/jbc.273.29.18288. PMID 9660793.

External links

Further reading

  • Farber JM (July 1990). "A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines". Proceedings of the National Academy of Sciences of the United States of America. 87 (14): 5238–42. doi:10.1073/pnas.87.14.5238. PMC 54298. PMID 2115167.
  • Liao F, Rabin RL, Yannelli JR, Koniaris LG, Vanguri P, Farber JM (November 1995). "Human Mig chemokine: biochemical and functional characterization". The Journal of Experimental Medicine. 182 (5): 1301–14. doi:10.1084/jem.182.5.1301. PMC 2192190. PMID 7595201.
  • Farber JM (April 1993). "HuMig: a new human member of the chemokine family of cytokines". Biochemical and Biophysical Research Communications. 192 (1): 223–30. doi:10.1006/bbrc.1993.1403. PMID 8476424.
  • Erdel M, Laich A, Utermann G, Werner ER, Werner-Felmayer G (1998). "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. doi:10.1159/000015043. PMID 9730616.
  • Jenh CH, Cox MA, Kaminski H, Zhang M, Byrnes H, Fine J, Lundell D, Chou CC, Narula SK, Zavodny PJ (April 1999). "Cutting edge: species specificity of the CC chemokine 6Ckine signaling through the CXC chemokine receptor CXCR3: human 6Ckine is not a ligand for the human or mouse CXCR3 receptors". Journal of Immunology. 162 (7): 3765–9. PMID 10201891.
  • Rabin RL, Park MK, Liao F, Swofford R, Stephany D, Farber JM (April 1999). "Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling". Journal of Immunology. 162 (7): 3840–50. PMID 10201901.
  • Shields PL, Morland CM, Salmon M, Qin S, Hubscher SG, Adams DH (December 1999). "Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver". Journal of Immunology. 163 (11): 6236–43. PMID 10570316.
  • Jinquan T, Jing C, Jacobi HH, Reimert CM, Millner A, Quan S, Hansen JB, Dissing S, Malling HJ, Skov PS, Poulsen LK (August 2000). "CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma". Journal of Immunology. 165 (3): 1548–56. doi:10.4049/jimmunol.165.3.1548. PMID 10903763.
  • Loetscher P, Pellegrino A, Gong JH, Mattioli I, Loetscher M, Bardi G, Baggiolini M, Clark-Lewis I (February 2001). "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. doi:10.1074/jbc.M005652200. PMID 11110785.
  • Romagnani P, Annunziato F, Lazzeri E, Cosmi L, Beltrame C, Lasagni L, Galli G, Francalanci M, Manetti R, Marra F, Vanini V, Maggi E, Romagnani S (February 2001). "Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) alphabeta+ CD8+ single-positive T cells, TCRgammadelta+ T cells, and natural killer-type cells in human thymus". Blood. 97 (3): 601–7. doi:10.1182/blood.V97.3.601. PMID 11157474.
  • Dwinell MB, Lügering N, Eckmann L, Kagnoff MF (January 2001). "Regulated production of interferon-inducible T-cell chemoattractants by human intestinal epithelial cells". Gastroenterology. 120 (1): 49–59. doi:10.1053/gast.2001.20914. PMID 11208713.
  • Lambeir AM, Proost P, Durinx C, Bal G, Senten K, Augustyns K, Scharpé S, Van Damme J, De Meester I (August 2001). "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. doi:10.1074/jbc.M103106200. PMID 11390394.
  • Stoof TJ, Flier J, Sampat S, Nieboer C, Tensen CP, Boorsma DM (June 2001). "The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells". The British Journal of Dermatology. 144 (6): 1114–20. doi:10.1046/j.1365-2133.2001.04220.x. PMID 11422029.
  • Campbell JD, Stinson MJ, Simons FE, Rector ES, HayGlass KT (July 2001). "In vivo stability of human chemokine and chemokine receptor expression". Human Immunology. 62 (7): 668–78. doi:10.1016/S0198-8859(01)00260-9. PMID 11423172.
  • Scapini P, Laudanna C, Pinardi C, Allavena P, Mantovani A, Sozzani S, Cassatella MA (July 2001). "Neutrophils produce biologically active macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19". European Journal of Immunology. 31 (7): 1981–8. doi:10.1002/1521-4141(200107)31:7<1981::AID-IMMU1981>3.0.CO;2-X. PMID 11449350.
  • Gillitzer R (August 2001). "Inflammation in human skin: a model to study chemokine-mediated leukocyte migration in vivo". The Journal of Pathology. 194 (4): 393–4. doi:10.1002/1096-9896(200108)194:4<393::AID-PATH907>3.0.CO;2-7. PMID 11523044.
  • Romagnani P, Rotondi M, Lazzeri E, Lasagni L, Francalanci M, Buonamano A, Milani S, Vitti P, Chiovato L, Tonacchera M, Bellastella A, Serio M (July 2002). "Expression of IP-10/CXCL10 and MIG/CXCL9 in the thyroid and increased levels of IP-10/CXCL10 in the serum of patients with recent-onset Graves' disease". The American Journal of Pathology. 161 (1): 195–206. doi:10.1016/S0002-9440(10)64171-5. PMC 1850693. PMID 12107104.