Alternative titles; symbols
HGNC Approved Gene Symbol: CCL25
Cytogenetic location: 19p13.2 Genomic coordinates (GRCh38): 19:8,052,341-8,062,650 (from NCBI)
Chemokines are a family of small cytokines that control the migration of leukocyte populations to localized sites of inflammation. Beta-chemokines are characterized by a CC motif (2 contiguous cysteines). To identify genes involved in T-cell development, Vicari et al. (1997) analyzed a cDNA library from the thymus of mice deficient in RAG1 (179615). They identified a cDNA with homology to beta-chemokines and designated it Teck for 'thymus-expressed chemokine.' The human TECK gene was cloned from a fetal small intestine cDNA library using the mouse Teck gene as a probe. The human TECK gene encodes a predicted 151-amino acid protein that is 49% identical to the mouse Teck protein. On Northern blots of human tissue, TECK was expressed as a 1.05-kb mRNA primarily in thymus and small intestine. In mouse thymus, Teck is produced by dendritic cells. Recombinant mouse Teck has chemotactic activity on thymocytes, macrophages, and dendritic cells.
Zaballos et al. (1999) showed that CCR9 (604738) is the receptor for TECK.
By RT-PCR and immunohistochemistry analyses, Papadakis et al. (2000) demonstrated that TECK is expressed in the small intestine but not the colon by endothelial cells and a subset of cells in intestinal crypts and the lamina propria, predominantly in areas with lymphocyte aggregates. In a chemotaxis assay, TECK attracted lamina propria mononuclear cells, most likely CCR9-positive T cells, from small bowel but not from colon, and failed to induce migration of peripheral blood cells. Papadakis et al. (2000) concluded that the TECK/CCR9 ligand/receptor pair is important for the selective homing and retention of CCR9-positive T cells to the small intestine rather than colon, and provides a mechanism for regional specialization of the mucosal immune system.
By screening splenic and intestinal lymphocytes for chemotaxis in response to a panel of chemokines, Bowman et al. (2002) determined that Ccl25 is a potent and selective chemoattractant for IgA-producing cells in mice. Mesenteric lymph node cells secreting IgA from mice infected with rotavirus migrated significantly more strongly to Ccl25 than to Sdf1 (600835).
Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to nonlymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha-4-beta-7 (192975, 147559) and CCR9, the receptor for the gut-associated chemokine TECK/CCL25. Mora et al. (2003) showed that this imprinting of gut tropism is mediated by dendritic cells from Peyer patches. Stimulation of CD8 (see 186910)-expressing T cells by dendritic cells from Peyer patches, peripheral lymph nodes, and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer patch dendritic cells induced high levels of alpha-4-beta-7, responsiveness to TECK, and the ability to home to the small intestine. Mora et al. (2003) concluded that their findings established that Peyer patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomic sites most likely to contain their cognate antigen.
Using flow cytometry, Eksteen et al. (2004) found substantially increased expression of CCR9 on liver-infiltrating lymphocytes (LILs) in patients with primary sclerosing cholangitis (PSC; see 109720) compared with organ donor controls and patients with other chronic inflammatory liver diseases. Immunohistochemical and Western blot analyses demonstrated that CCL25, which is normally expressed in thymus and intestine only, was highly expressed in livers of PSC patients but not other liver disease patients. In vitro, CCR9-positive LILs preferentially migrated to CCL25 and could be triggered by CCL25 to bind immobilized MADCAM1 (102670) via alpha-4/beta-7 integrins. Eksteen et al. (2004) proposed that T cells activated in the gut during active inflammatory bowel disease (see IBD1; 266600) differentiate into effector cells with the ability to bind to both hepatic and mucosal endothelium. They suggested that CCL25 and MADCAM1 cooperate in recruiting mucosal CCR9-positive lymphocytes to the liver in PSC.
Vicari et al. (1997) mapped the mouse Teck gene to chromosome 8 by interspecific backcross, in a region that is syntenic with human 19p13.3 and 13q34. By somatic cell hybridization, radiation hybrid analysis, and fluorescence in situ hybridization, Nomiyama et al. (1998) mapped the human SCYA25 gene to 19p13.2.
Bowman, E. P., Kuklin, N. A., Youngman, K. R., Lazarus, N. H., Kunkel, E. J., Pan, J., Greenberg, H. B., Butcher, E. C. The intestinal chemokine thymus-expressed chemokine (CCL25) attracts IgA antibody-secreting cells. J. Exp. Med. 195: 269-275, 2002. [PubMed: 11805153] [Full Text: https://doi.org/10.1084/jem.20010670]
Eksteen, B., Grant, A. J., Miles, A., Curbishley, S. M., Lalor, P. F., Hubscher, S. G., Briskin, M., Salmon, M., Adams, D. H. Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis. J. Exp. Med. 200: 1511-1517, 2004. [PubMed: 15557349] [Full Text: https://doi.org/10.1084/jem.20041035]
Mora, J. R., Bono, M. R., Manjunath, N., Weninger, W., Cavanagh, L. L., Rosemblatt, M., von Andrian, U. H. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424: 88-93, 2003. [PubMed: 12840763] [Full Text: https://doi.org/10.1038/nature01726]
Nomiyama, H., Amano, K., Kusuda, J., Imai, T., Miura, R., Yoshie, O., Matsuda, Y. The human CC chemokine TECK (SCYA25) maps to chromosome 19p13.2. Genomics 51: 311-312, 1998. [PubMed: 9722960] [Full Text: https://doi.org/10.1006/geno.1998.5352]
Papadakis, K. A., Prehn, J., Nelson, V., Cheng, L., Binder, S. W., Ponath, P. D., Andrew, D. P., Targan, S. R. The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system. J. Immun. 165: 5069-5076, 2000. [PubMed: 11046037] [Full Text: https://doi.org/10.4049/jimmunol.165.9.5069]
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., Zlotnik, A. TECK: a novel CC chemokine specifically expressed by thymic dendritic cells and potentially involved in T cell development. Immunity 7: 291-301, 1997. [PubMed: 9285413] [Full Text: https://doi.org/10.1016/s1074-7613(00)80531-2]
Zaballos, A., Gutierrez, J., Varona, R., Ardavin, C., Marquez, G. Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as CCR9, the receptor for the chemokine TECK. J. Immun. 162: 5671-5675, 1999. [PubMed: 10229797]