Alternative titles; symbols
HGNC Approved Gene Symbol: CCL22
Cytogenetic location: 16q21 Genomic coordinates (GRCh38): 16:57,357,909-57,366,189 (from NCBI)
Chemokines, a family of secreted proteins that attract and activate a variety of cell types and enhance the immune response, are classified into 2 subfamilies based on the relative positions of the first 2 of 4 conserved cysteine residues. The CC chemokines, in which the first 2 cysteines are adjacent, usually act on monocytes, T lymphocytes, and, in some cases, eosinophils, basophils, or mast cells. The CC subfamily proteins are 70 to 100 amino acids long, have 25 to 75% identity with each other, and include SCYA5/RANTES (187011), SCYA3/MIP1-alpha (182283), and SCYA4/MIP1-beta (182284). Godiska et al. (1997) isolated a novel member of the CC chemokine subfamily, designated SCYA22, by random sequencing of cDNA clones from a monocyte-derived macrophage library. The full-length SCYA22 cDNA clone, termed MDC (monocyte-derived chemokine) by the authors, contains an open reading frame of 93 amino acids. The SCYA22 protein shares 28 to 34% identity with other CC chemokines and contains the characteristic 4-cysteine motif and 9 other highly conserved residues. Northern blot analysis indicated high expression of SCYA22 in macrophages and in monocyte-derived dendritic cells, but not in monocytes, natural killer cells, or several cell lines of epithelial, endothelial, or fibroblast origin. In human tissues, high expression of SCYA22 mRNA was detected in thymus and lower expression in lung and spleen.
Godiska et al. (1997) found that dendritic cells and IL2 (147680)-activated natural killer cells demonstrated chemotactic response to SCYA22, whereas neutrophils did not.
By receptor binding analysis, Imai et al. (1998) determined that CCR4 (604836), a receptor for SCYA17 (601520), is also a receptor for SCYA22. SCYA17 and SCYA22 competed with a fusion protein for CCR4 binding, while no binding competition was observed for SCYA2 (158105), SCYA3, SCYA4, SCYA5, SCYA7 (158106), and SCYA13 (601391).
Human T-lymphotropic virus (HTLV)-1 is a persistent retrovirus estimated to infect 10 to 20 million people. The majority of infected individuals are asymptomatic carriers, but 1 to 3% of infected individuals develop progressive inflammation of the central nervous system (see 159580), and about 4% of seropositive individuals develop a malignant lymphoproliferative disorder called adult T-cell leukemia/lymphoma (ATLL). Toulza et al. (2010) found that there was a high concentration of plasma CCL22 in HTLV-1-infected individuals and that the concentration was strongly correlated with the frequency of FOXP3 (300292)-positive cells, which express CCR4. CCL22 was produced by cells that expressed the HTLV-1 transactivator protein Tax, and the increased CCL22 enhanced the migration and survival of FOXP3-positive cells in vitro. Toulza et al. (2010) concluded that HTLV-1-induced CCL22 causes the high frequency of FOXP3-positive cells observed in HTLV-1 infection and that FOXP3-positive cells may both retard the progression of ATLL and HTLV-1-associated inflammatory diseases and contribute to the immune suppression seen in HTLV-1 infection.
By PCR screening of genomic DNA from mouse-human and hamster-human chimeric cell lines, Godiska et al. (1997) mapped the SCYA22 gene to chromosome 16. Nomiyama et al. (1998) demonstrated that the SCYA22 gene is clustered on 16q13 with the SCYD1 (601880) and SCYA17 genes. This was determined by analyzing somatic cell hybrids containing various portions of human chromosome 16 with PCR. Further study of BAC clones demonstrated that the 3 genes are located within a short segment, probably 200 kb or less. This supported their close evolutionary relationship. By FISH, Imai et al. (1998) confirmed the localization of SCYA22 to 16q13.
Godiska, R., Chantry, D., Raport, C. J., Sozzani, S., Allavena, P., Leviten, D., Mantovani, A., Gray, P. W. Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells. J. Exp. Med. 185: 1595-1604, 1997. [PubMed: 9151897] [Full Text: https://doi.org/10.1084/jem.185.9.1595]
Imai, T., Chantry, D., Raport, C. J., Woods, C. L., Nishimura, M., Godiska, R., Yoshie, O., Gray, P. W. Macrophage-derived chemokine is a functional ligand for the CC chemokine receptor 4. J. Biol. Chem. 273: 1764-1768, 1998. [PubMed: 9430724] [Full Text: https://doi.org/10.1074/jbc.273.3.1764]
Nomiyama, H., Imai, T., Kusuda, J., Miura, R., Callen, D. F., Yoshie, O. Human chemokines fractalkine (SCYD1), MDC (SCYA22) and TARC (SCYA17) are clustered on chromosome 16q13. Cytogenet. Cell Genet. 81: 10-11, 1998. [PubMed: 9691168] [Full Text: https://doi.org/10.1159/000015000]
Toulza, F., Nosaka, K., Tanaka, Y., Schioppa, T., Balkwill, F., Taylor, G. P., Bangham, C. R. M. Human T-lymphotropic virus type 1-induced CC chemokine ligand 22 maintains a high frequency of functional FoxP3+ regulatory T cells. J. Immun. 185: 183-189, 2010. [PubMed: 20525891] [Full Text: https://doi.org/10.4049/jimmunol.0903846]