Alternative titles; symbols
HGNC Approved Gene Symbol: CXCL11
Cytogenetic location: 4q21.1 Genomic coordinates (GRCh38) : 4:76,033,682-76,036,070 (from NCBI)
Chemokines are essential mediators of normal leukocyte trafficking as well as of leukocyte recruitment during inflammation. The CXC subfamily is divided into ELR (glu-leu-arg) and non-ELR CXC chemokines based on the presence or absence of this tripeptide sequence adjacent to the CXC motif. CXCL11 is a non-ELR chemokine that is highly expressed in cytokine-stimulated astrocytes (Cole et al., 1998).
By screening an astrocytoma cell line for genes induced by gamma-interferon (IFNG; 147570), Rani et al. (1996) identified a partial cDNA encoding SCYB11, which they called beta-R1. Northern blot analysis detected a single SCYB11 transcript of 4.5 kb.
Using a novel yeast-based system to screen an activated peripheral blood mononuclear cell library for cDNAs encoding secreted proteins, Jacobs et al. (1997) identified a cDNA encoding SCYB11, which they termed H174. The SCYB11 gene encodes a 94-amino acid protein.
By searching for novel sequences in a cDNA library constructed from primary astrocytes stimulated with IFNG and other proinflammatory cytokines, Cole et al. (1998) obtained a full-length cDNA encoding SCYB11, which they called ITAC (interferon-inducible T-cell alpha-chemoattractant). The SCYB11 gene encodes a predicted 94-amino acid non-ELR CXC cytokine containing a 21-amino acid signal peptide. Northern blot analysis detected a 1.4-kb SCYB11 transcript at highest levels in peripheral blood leukocytes, pancreas, and liver, followed by thymus, spleen, and lung. Lower levels were detected in placenta, prostate, and small intestine. A 4.5-kb SCYB11 transcript was also detected in pancreas, peripheral blood leukocytes, and spleen.
Rani et al. (1996) found that the SCYB11 gene was strongly induced by IFNG and beta-interferon (IFNB; 147640), but only weakly induced by alpha-interferon (IFNA; 147660). Induction of SCYB11 required expression of STAT1 (600555).
Cole et al. (1998) found that SCYB11 induced a chemotactic response in activated T cells but not in fresh T cells, monocytes, or granulocytes. By cross-desensitization and binding analyses, Cole et al. (1998) showed that SCYB11, like SCYB9 (MIG; 601704) and SCYB10 (147310), uses the T-cell-restricted CXC receptor-3 (CXCR3, or GPR9; 300574). They found that SCYB11 has a higher affinity for CXCR3 than do SCYB9 and SCYB10. IFNG upregulated SCYB11 expression in astrocytes, monocytes, and microglial cells. Interleukin-1 (see IL1A; 147760) synergized with IFNG in inducing SCYB11 expression in astrocytes. The authors found that SCYB11 is more potent than SCYB9 and SCYB10 in inducing increases in intracellular calcium levels.
Luo et al. (1998) found that monocyte chemotaxis occurs in response to recombinant SCYB11. RT-PCR analysis detected SCYB11 expression in brain tissue from a patient with AIDS dementia and a patient with multiple sclerosis but not in 2 controls.
In a study to identify biologically active chemokines produced by keratinocytes, Tensen et al. (1999) identified SCYB11, which they called IP9 (IFNG-inducible protein-9). Northern blot analysis detected SCYB11 expression in keratinocytes stimulated by IFNG. RNA in situ hybridization analysis detected SCYB11 expression in basal layer keratinocytes in allergic patch test reactions, lichen planus lesions, and mycosis fungoides. SCYB11 expression was detected particularly in areas showing epidermal infiltration by activated T cells but not in normal skin or unchallenged skin of allergic patients.
Because type I IFNs are critical for regulation of osteoclastogenesis in mice, Coelho et al. (2005) compared the effects of IFNA2 (147562) and IFNB on differentiation of human monocytes into osteoclasts. Although primary monocytes undergoing osteoclastic differentiation were highly and equally sensitive to both proteins, IFNB was 100-fold more potent than IFNA2 at inhibiting osteoclastogenesis. Microarray and RT-PCR analyses showed that CXCL11 was the only gene differentially upregulated in this cellular system by IFNB compared with IFNA2. Treatment of monocytes with CXCL11 inhibited osteoclastic differentiation, and CXCL11 acted through a receptor distinct from CXCR3 and not through antagonism of CCR5 (601373). Coelho et al. (2005) proposed that IFNB may have clinical relevance in preventing osteolysis.
Using cellular, molecular, biologic, and pharmacologic assessments, Burns et al. (2006) identified CXCR7 (610376) as an alternative receptor for SDF1 (CXCL12; 600835) and ITAC. Flow cytometric and Northern blot analyses showed that CXCR7 was highly expressed in mouse and human transformed cells, endothelial cells, and embryonic tissue.
By sequence analysis of a genomic clone encoding SCYB11, Tensen et al. (1999) found that, like SCYB10, the SCYB11 gene contains 4 exons. Exon 1 encodes the 21-amino acid signal peptide, and the remaining exons encode 43-, 24-, and 7-amino acid sequences, respectively.
By PCR analysis of somatic cell hybrids, Cole et al. (1998) mapped the SCYB11 gene to chromosome 4. Erdel et al. (1998) mapped the SCYB11 gene to 4q21.2 using FISH. By PCR analysis and mapping of YAC clones, O'Donovan et al. (1999) localized the genes for a number of CXC chemokines to 4q12-q21. They proposed that the order in this region is centromere--IL8 (146930)--GRO1 (155730)/PPBP (121010)/PF4 (173460)--SCYB5 (600324)/SCYB6 (138965)--GRO2 (139110)/GRO3 (139111)--SCYB11--SCYB10--MIG--telomere.
Burns, J. M., Summers, B. C., Wang, Y., Melikian, A., Berahovich, R., Miao, Z., Penfold, M. E. T., Sunshine, M. J., Littman, D. R., Kuo, C. J., Wei, K., McMaster, B. E., Wright, K., Howard, M. C., Schall, T. J. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J. Exp. Med. 203: 2201-2213, 2006. [PubMed: 16940167] [Full Text: https://doi.org/10.1084/jem.20052144]
Coelho, L. F. L., Magno de Freitas Almeida, G. M. F., Mennechet, F. J. D., Blangy, A., Uze, G. Interferon-alpha and -beta differentially regulate osteoclastogenesis: role of differential induction of chemokine CXCL11 expression. Proc. Nat. Acad. Sci. 102: 11917-11922, 2005. [PubMed: 16081539] [Full Text: https://doi.org/10.1073/pnas.0502188102]
Cole, K. E., Strick, C. A., Paradis, T. J., Ogborne, K. T., Loetscher, M., Gladue, R. P., Lin, W., Boyd, J. G., Moser, B., Wood, D. E., Sahagan, B. G., 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. J. Exp. Med. 187: 2009-2021, 1998. [PubMed: 9625760] [Full Text: https://doi.org/10.1084/jem.187.12.2009]
Erdel, M., Laich, A., Utermann, G., Werner, E. R., 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). Cytogenet. Cell Genet. 81: 271-272, 1998. [PubMed: 9730616] [Full Text: https://doi.org/10.1159/000015043]
Jacobs, K. A., Collins-Racie, L. A., Colbert, M., Duckett, M., Golden-Fleet, M., Kelleher, K., Kriz, R., LaVallie, E. R., Merberg, D., Spaulding, V., Stover, J., Williamson, M. J., McCoy, J. M. A genetic selection for isolating cDNAs encoding secreted proteins. Gene 198: 289-296, 1997. [PubMed: 9370294] [Full Text: https://doi.org/10.1016/s0378-1119(97)00330-2]
Luo, Y., Kim, R., Gabuzda, D., Mi, S., Collins-Racie, L. A., Lu, Z., Jacobs, K. A., Dorf, M. E. The CXC-chemokine, H174: expression in the central nervous system. J. Neurovirol. 4: 575-585, 1998. [PubMed: 10065899] [Full Text: https://doi.org/10.3109/13550289809114224]
O'Donovan, N., Galvin, M., Morgan, J. G. Physical mapping of the CXC chemokine locus on human chromosome 4. Cytogenet. Cell Genet. 84: 39-42, 1999. [PubMed: 10343098] [Full Text: https://doi.org/10.1159/000015209]
Rani, M. R. S., Foster, G. R., Leung, S., Leaman, D., Stark, G. R., Ransohoff, R. M. Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha. J. Biol. Chem. 271: 22878-22884, 1996. [PubMed: 8798467] [Full Text: https://doi.org/10.1074/jbc.271.37.22878]
Tensen, C. P., Flier, J., Rampersad, S. S., Sampat-Sardjoepersad, S., Scheper, R. J., Boorsma, D. M., Willemze, R. Genomic organization, sequence and transcriptional regulation of the human CXC 11 gene. Biochim. Biophys. Acta 1446: 167-172, 1999. [PubMed: 10395932] [Full Text: https://doi.org/10.1016/s0167-4781(99)00084-6]
Tensen, C. P., Flier, J., van der Raaij-Helmer, E. M. H., Sampat-Sardjoepersad, S., van der Schors, R. C., Leurs, R., Scheper, R. J., Boorsma, D. M., Willemze, R. Human IP-9: a keratinocyte-derived high affinity CXC-chemokine ligand for the IP-10/Mig receptor (CXCR3). J. Invest. Derm. 112: 716-722, 1999. [PubMed: 10233762] [Full Text: https://doi.org/10.1046/j.1523-1747.1999.00581.x]