TECK/CCL25 Daniel J. Catron and Albert Zlotnik* Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Inc., 901 California Avenue, Palo Alto, CA 94304-1104, USA * corresponding author tel: 650 496-1131, fax: 650 496-1200, e-mail:
[email protected] DOI: 10.1006/rwcy.2000.11018.
SUMMARY
Alternative names
TECK/CCL25 (thymus-expressed chemokine) is expressed in a highly specific fashion by thymic stromal cells and at lower levels in the small intestine. It is probably involved in T cell development and/or in thymic architecture. It is classified in the CC or subfamily of chemokines. It is now designated CCL25 according to the new chemokine nomenclature. TECK/CCL25 is chemotactic for activated macrophages, thymocytes, and perhaps dendritic cells in vitro. Mouse TECK/CCL25 is located on chromosome 8 and human TECK/CCL25 is located in a syntenic region in chromosome 19p13.2. It is produced by thymic dendritic cells and epithelial cells. CCR9, formerly known as GPR9-6, has been identified as the TECK/CCL25 receptor.
TECK/CCL25 is now designated CCL25 according to the new chemokine nomenclature.
BACKGROUND
Human TECK/CCL25: U86358 Mouse TECK/CCL25: U86357
TECK/CCL25 is a CC or chemokine that was discovered by random sequencing of a cDNA library derived from the thymus of a RAG-1 knockout mouse (Vicari et al., 1997). This chemokine is highly expressed in the thymus, but not expressed in other tissues. However, low but significant expression was observed in the small intestine. The human homolog of TECK/CCL25 was cloned from a human small intestine cDNA library (Vicari et al., 1997). This pattern of expression strongly suggests that TECK/ CCL25 plays a role in T cell development.
Discovery TECK/CCL25 was discovered by random sequencing of a cDNA library derived from the thymus of a RAG-1 knockout mouse.
Main activities and pathophysiological roles TECK/CCL25 has been shown to be chemotactic for activated macrophages, thymocytes, and perhaps dendritic cells in vitro (Zaballos et al., 1999).
GENE AND GENE REGULATION
Accession numbers
Chromosome location Mouse TECK/CCL25 is located in mouse chromosome 8 (Vicari et al., 1997), while human TECK/ CCL25 is located in a syntenic region in human chromosome 19p13.2 (Nomiyama et al., 1998). TECK/CCL25 is the first chemokine that maps to this location, away from other CC chemokine clusters.
Cells and tissues that express the gene TECK/CCL25 is produced by thymic dendritic cells (Vicari et al., 1997) and epithelial cells (Wilkinson
1282 Daniel J. Catron and Albert Zlotnik et al., 1999). The identity of the cells expressing TECK/CCL25 in the small intestine is unknown.
RECEPTOR UTILIZATION Its receptor is the previous orphan GPCR known as GPR9-6, now renamed CCR9 (Zaballos et al., 1999). CCR9 expression closely parallels the expression of TECK/CCL25, being highest in the thymus and low or absent in most other tissues. Significantly, it was detected in both lymph nodes and spleen (Zaballos et al., 1999), while TECK/CCL25 was only detected in spleen following lipopolysaccharide injection (Vicari et al., 1997).
PROTEIN
Sequence See Figure 1.
Description of protein
IN VITRO ACTIVITIES
TECK/CCL25 has 142 amino acids, which means that it is about 40 amino acids longer than other `typical' CC chemokines. One of the most closely related chemokines is TARC/CCL17, which is also produced by dendritic cells and is highly expressed in the thymus (Vicari et al., 1997). The possible function of the C-terminus tail of TECK/CCL25 is unknown. It is also unknown whether this `tail' is necessary for TECK/CCL25 function.
In vitro findings TECK/CCL25 chemoattracts thymocytes and macrophages in vitro. Immature thymocytes may respond better.
Bioassays used Both Boyden chamber and chemotaxis transwell assays were used.
Important homologies TECK/CCL25 shares various degrees of homology with a number of CC chemokines. The closest related chemokine is ALC/CTACK (CCL27).
CELLULAR SOURCES AND TISSUE EXPRESSION
IN VIVO BIOLOGICAL ACTIVITIES OF LIGANDS IN ANIMAL MODELS
Normal physiological roles Probably involved in T cell development.
Cellular sources that produce
Species differences
Strong expression in the thymus by thymic stromal cells and in low but detectable expression in the small intestine. No other expression detected so far.
Two clearly related genes encode homologs of CCL25 in both mouse and human. Expression pattern is similar, suggesting similar function.
Figure 1 CCL25.
Amino acid sequences for human and mouse TECK/
Human TECK (hCCL25) MNLWLLACLV AGFLGAWAPA VHTQGVFEDC CLAYHYPIGW AVLRRAWTYR IQEVSGSCNL PAAIFYLPKR HRKVCGNPKS REVQRAMKLL DARNKVFAKL HHNMQTFQAG PHAVKKLSSG NSKLSSSKFS NPISSSKRNV SLLISANSGL SDSQTERKKS NHMKSKVENP NSTSVRSATL GHPRMVMMPR KTNN Mouse TECK (mCCL25) MKLWLFACLV ACFVGAWMPV VHAQGAFEDC CLGYQHRIKW NVLRHARNYH QQEVSGSCNL RAVRFYFRQK VVCGNPEDMN VKRAIRILTA RKRLVHWKSA
TECK/CCL25 1283
PATHOPHYSIOLOGICAL ROLES IN NORMAL HUMANS AND DISEASE STATES AND DIAGNOSTIC UTILITY
Normal levels and effects Unknown; probably no detectable levels under normal conditions. Produced constitutively in the thymus and small intestine.
Role in experiments of nature and disease states Probably involved in T cell development and/or in thymic architecture. Its role is unknown in the small intestine.
References Nomiyama, H., Amano, K., Kusuda, J., Imai, T., Miura, R., Yoshie, O., and Matsuda, Y. (1998). The human CC chemokine TECK (SCYA25) maps to chromosome 19p13.2. Genomics 51, 311±312. Vicari, A. P., Figueroa, D. J., Hedrick, J. A., Foster, J. S., Singh, K. P., Menon, S., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Bacon, K. B., and Zlotnik, A. (1997). TECK: a novel CC chemokine specifically expressed by thymic dendritic cells and potentially involved in T cell development. Immunity 7, 291±301. Wilkinson, B., Owen, J. J., and Jenkinson, E. J. (1999). Factors regulating stem cell recuitment to the fetal thymus. J. Immunol. 162, 3873±3881. Zaballos, A., Gutierrez, J., Varona, R., Ardavin, C., and Marquez, G. (1999). Cutting edge: identification of the orphan chemokine receptor GPR9-6 as CCR9, the receptor for the chemokine TECK. J. Immunol. 162, 5671±5675.
