Cxcl11

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, some virus types and bacteria. In humans, about 50 chemokines are currently known. A strongly conserved structural feature of all chemokines is a fixed group of cysteine residues that is stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for its fixed 3-dimensional structure (see below chemokines).

In the CC-chemokines the cysteines follow each other directly (see figure), in the CXC-chemokines they are separated by 1, in the CXXXC-chemokines by 3 other amino acids. Chemokines are produced and secreted by a large number of immune cells. They mediate their signals by means of specific chemokine receptors via G-proteins. The fact that chemokines and their receptors are not only expressed on inflammatory cells, but also by epithelial cells, mesenchymal cells, neurogenic cells, endothelial cells, and various tumor cell lines, suggests that they participate in numerous regulatory cell functions.

CXCL11, also C-X-C motif chemokine 11 or interferon-inducible T-cell alpha chemoattractant or I-TAC is a small, inflammatory chemokine from the group of CXC chemokines, which is produced and secreted by various cell systems, often interferon-alpha and -gamma triggered. Thus, the chemokine is very prominently expressed in peripheral leukocytes, pancreas and liver parenchyma. In smaller amounts it is expressed in thymus, spleen, lung, small intestine and prostate tissue.

The chemokine is encoded by the CXCL11 gene, which in humans is located on chromosome 4q21.1 together with the genes for CXCL9 and CXCL10 .

Like the homologous chemokines CXCL9 and CXCL10, CXCL11 binds to the G-protein-coupled chemokine receptor CXCR3 and has a chemotactic effect on T cells, but not on neutrophil granulocytes. The CXCR3 receptor is also expressed in pneumocytes and pulmonary and hepatic fibroblasts. A variant of the CXCR3 receptor has been described, which has been named CXCR3-B (the previously known CXCL3 receptor is to be named CXCL3A in the future). CXCL3B mediates the angiostatic activity of CXCR3 ligands and also acts as a functional receptor for CXCL4. Furthermore, CXCL11 binds to the chemokine receptor "CXCR7".

CXCL11 is secreted by numerous cells, including monocytes, neutrophil granulocytes, endothelial cells, keratinocytes, mesenchymal cells, dendritic cells, hepatocytes, thyrocytes, astrocytes and fibroblasts. The chemokine acts as an attractor for monocytes/macrophages, T cells, NK cells, eosinophil granulocytes and dendritic cells. It is involved in antitumor activities, in immunological antiviral and antibacterial reactions, in the inhibition of neoangiogenesis and bone marrow proliferation.

Neuroborreliosis: In neuroborreliosis, the chemokines CXCL11, CXCL10, CXCL9, CXCL12, CXCL13 were clearly elevated both in the serum and in the cerebrospinal fluid before therapy, with decreasing values during and after antibiotic treatment, an indication of the pathogenetic significance of these chemokines

Multiple sclerosis: It has been shown that the CXCL11/CXCR3 axis is upregulated in relapsing-remitting MS. In a 1-year therapy study with natalizumab, it was shown that the pro-inflammatory cytokines such as: interleukin-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α together with the chemokines CXCL11, CXCL10, CXCL9, CCL17 and CCL22 were significantly reduced. From these results, clear relationships between the extent of cytokine expressions and the activity level of MS can be derived. Such correlations are not disease-specific, but are also to be expected in other TH1-associated inflammations.

Heart failure and left ventricular dysfunction: CXCL11 and the homologous chemokines CXCL-9 and CXCL-10 have been shown to be valid biomarkers for the development of heart failure and left ventricular dysfunction.

1. Antonelli A et al (2013) Interferon-α, -β and -γ induce CXCL11 secretion in human thyrocytes: modulation by peroxisome proliferator-activated receptor γ agonists. Immunobiology 218:690-659.
2. Basset L et al(2015) Interleukin-27 and IFNγ regulate the expression of CXCL9, CXCL10, and CXCL11 in hepatitis. J Mol Med (Berl) 93(12):1355-67.
3. Liang Y et al (2017) Serum Monokine Induced by Gamma Interferon Is Associated With Severity of Coronary Artery Disease. Int Heart J 58:24-29.
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5. Torraca V et al(2015)The CXCR3-CXCL11 signaling axis mediates macrophage recruitment and dissemination of mycobacterial infection. The Model Mech 8:253-269.
6. Rupertus K et al;(2014) Interaction of the chemokines I-TAC (CXCL11) and SDF-1 (CXCL12) in the regulation of tumor angiogenesis of colorectal cancer. Clin Exp Metastasis 31:447-459.
7. Vazirinejad R et al(2014) The Biological Functions, Structure and Sources of CXCL10 and Its Outstanding Part in the Pathophysiology of Multiple Sclerosis. Neuroimmunomodulation 21:322-330