CXC ligand 9

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CXC ligand 9
Properties of human protein
Mass / length primary structure 103 amino acids
Identifier
Gene name CXCL9
External IDs
Occurrence
Parent taxon Mammals

CXC-Ligand 9 (short: CXCL9 or MIG for English monokine induced by gamma interferon ) is a protein in mammals . Together with CXCL10 and CXCL11 it forms a group of homologous chemokines (messenger substances). These messenger substances are mainly produced by macrophages as part of an inflammatory reaction . They play a role in the activation of T lymphocytes and thus the activation of the immune system .

Mode of action

Macrophages secrete the messenger substance CXCL9 after stimulation with the pro-inflammatory cytokine interferon-γ. In addition, CXCL9 can be secreted by neutrophils to a lesser extent . However, stimulation with interferon-γ alone is not sufficient for this. The anti-inflammatory interleukins IL-4 and IL-10 suppress the expression of CXCL9 in neutrophils. The chemokine binds the G-protein coupled receptor CXCR3 (CXC receptor 3). As a result, cells of the immune defense that present CXCR3, such as T H 1 lymphocytes and NK cells , are able to chemotactically follow a concentration gradient of CXCL9.

Locality and classification

The gene ScyB9 ( small secreted cytokine B ) coding for CXCL9 is in close proximity to the genes for CXCL10 and CXCL11 in the chromosomal region 4q21. The location apart from the CXC chemokine cluster at 4q13, which contains significantly more genes, illustrates the greater relationship between these three chemokines. A signal sequence 22 amino acids long is cleaved off at the N-terminal of the propeptide encoded by ScyB9 . The secreted form comprises 103 amino acids with a calculated molar mass of 11.7  kDa . Because of the lack of a glutamyl-leucyl-arginine motif (ELR), CXCL9 is classified as a non-ELR CXC chemokine.

Polarization of the acquired immune response

CXCL9, CXCL10 and CXCL11 bind the common receptor CXCR3. This is predominantly expressed by T H 1 lymphocytes after activation with IL-2 or by natural killer cells. In contrast to other chemokines, CXCL9, CXCL10 and CXCL11 are not able to activate leukocytes via more than one receptor. By binding the CC chemokine receptor CCR3, they prevent activation of T H 2 lymphocytes, which predominantly present this receptor. In this way, CXCL9, like CXCL10 and CXCL11, promotes polarization in favor of a pro-inflammatory, T H 1 -mediated immune response .

Individual evidence

  1. ↑ Homologues at OMA
  2. ↑ Farber, JM (1990): A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. PNAS 87 (14): 5238-42.
  3. ↑ a b Gasperini, S. et al. (1999): Gene expression and production of the monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10) chemokines by human neutrophils. J Immunol. 162 (8): 4928-37.
  4. ↑ Zlotnik, A., Yoshie, O., (2000): Chemokines: a new classification system and their role in immunity. Immunity 12 (2): 121-7.
  5. ↑ Loetscher, M. et al. (1996): Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med . 184 (3): 963-9.
  6. ↑ Inngjerdingen, M. et al. (2001): Expression and regulation of chemokine receptors in human natural killer cells. Blood 97 (2): 367-75.
  7. ↑ Loetscher, M. et al. (2001): The ligands of CXC chemokine receptor 3, I-TAC, Mig, and IP10, are natural antagonists for CCR3. J Biol Chem . 276 (5): 2986-91.

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