About I-TAC / CXCL11:
Mechanism
● CXCL11 is a relatively small cytokine. As its name suggests, it is also a member of the CXC chemokine family. This family is also known as I-TAC (Interferon-inducible T-cell alpha chemoattractant) or IP-9 (Interferon gamma-inducible protein 9).
● CXCL11 is expressed in peripheral blood leukocytes, and is found in the pancreas, liver, thymus, lungs, and spleen. Smaller expression levels are also found in the placenta, prostate, and small intestine.
● As with other chemokines, CXCL11 is involved in the recruitment of leukocytes during inflammatory response.
● CXCL11 is part of the following gene families: chemokine ligands, endogenous ligands.
Structure
● The gene contains 4 exons.
● Exon 1 encodes 21-amino acid signal peptides
● The remaining exons encode 43-, 24-, and 7-amino acid sequences.
● The CXCL11 gene is, like other members of the CXC chemokine family, located on human chromosome 4.
Function
● CXCL11 induces a chemotactic response in activated T cells, but not in fresh T cells. Furthermore, it also does not induce a chemotactic response in monocytes or granulocytes.
● CXCL11 is more potent than SCYB9 and SCYB10 when inducing increases in intracellular calcium levels.
● Monocyte chemotaxis occurs in response to recombinant CXCL11.
● In mice studies, it has been found that CXCL11 is the only gene differentially upregulated by IFNB compared with IFNA2.
● Further studies also found that treatment of monocytes with CXCL11 inhibited osteoclastic differentiation.
● CXCL11 expression has also been identified in keratinocytes that have been stimulated by IFNG.
● RNA in situ hybridization analysis also detected CXCL11 express in allergic patch test reasons, mycosis fungoides, and lichen planus lesions. In particular, CXCL11 was detected in areas that showed epidermal infiltrated by activated T cells.
● Conversely, CXCL11 was not found in normal skin or skin of allergic patients that was otherwise unchallenged.
Interactions
● Gene expression in CXCL11 is induced by numerous Interferon, including IFN-γ, IFN-β, and IFN-α.
● CXCL11 interacts with cell surface chemokine receptor CXCR3 (predominantly)
● CXCL11 is also chemotactic for activated T cells
Significant notes
● Intriguingly, CXCL11 has been proven to be a valid biomarker for the development of both heart failure and left ventricular dysfunction.
● This link has also been established with fellow-family members such as CXCL9 and CXCL10.
● This has led to the suggestion that there is a pathophysiological relation between the levels of these specific chemokines and the development of heart issues. This is an area that is ripe for future study and research.