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Gene Review

XCL1  -  chemokine (C motif) ligand 1

Homo sapiens

Synonyms: ATAC, C motif chemokine 1, Cytokine SCM-1, LPTN, LTN, ...
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Disease relevance of XCL1

  • To identify a specific receptor for SCM-1 proteins, we produced recombinant SCM-1alpha and SCM-1beta by the baculovirus expression system and tested them on murine L1.2 cells stably expressing eight known chemokine receptors and three orphan receptors [1].
  • CD4(+) T-cell proliferation was completely restored by exogenous IL-2 or reversed by pertussis toxin, wortmannin, and genistein, suggesting the involvement of multiple partners in Lptn signaling [2].
  • Comparison of this material with that expressed in E. coli reveals that glycosylation significantly increases the biologic activity of XCL1 [3].
  • In the present study, the recombinant adenovirus vectors encoding chemokine CCL19 or XCL1 in an E1 cassette (AdRGD-mCCL19 and AdRGD-mXCL1) were developed [4].
  • However, PHA-driven production of both chemokines was significantly higher in LTNP, suggesting that in vivo activating stimuli might curtail HIV replication by inducing these chemokines [5].

Psychiatry related information on XCL1

  • METHODS: Plasma IL-7 levels were measured, by enzyme-linked immunoassay, in patients with primary, chronic, or long-term nonprogressive HIV-1 infection (PHI, CHI, and LTNP, respectively) before and after 40-48 weeks of antiretroviral therapy (ART) [6].

High impact information on XCL1

  • Studies of events associated with primary HIV infection, examination of lymphoid tissue at various stages of disease, and dissection of the immunologic and virologic components of LTNP should contribute substantially to our understanding of the pathogenesis of HIV disease [7].
  • Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial [8].
  • LTNP patients had undetectable viral loads, normal CD4+ T cell levels, and virus-specific cellular responses in peripheral blood and mucosal compartments [9].
  • We demonstrate that the maintenance of mucosal T cells, virus-specific responses, and distinct gene expression profiles correlate with clinical outcome in LTNP patients [9].
  • Microarray analysis revealed a significant increase in gene expression regulating immune activation, cell trafficking, and inflammatory response in intestinal mucosa of HVL patients as compared to LTNP patients [9].

Chemical compound and disease context of XCL1


Biological context of XCL1


Anatomical context of XCL1


Associations of XCL1 with chemical compounds

  • Population was divided in two groups: Group 1--Long Term Non Progressors (LTNP) includes 10 patients with B1-B2 CDC disease classification and with a less aggressive therapy (only 2 in HAART); Group 2--Rapid Progressors (RP) includes 9 patients with C3 disease classification [18].
  • Lymphotactin (Ltn), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta were all rapidly induced and sensitive to cyclosporine treatment [19].
  • In phorbol myristate acetate/ionomycin-stimulated PBMCs, ATAC/Lptn expression was detected in CD8+ T cells and in a significantly increased proportion of CD4+,CD28- T cells from RA patients as compared with healthy controls [15].
  • Lymphotactin (Lptn) is a new protein belonging to the C or gamma subfamily of chemokines with only two of the four cysteine residues [17].
  • Unmodified ATAC is a cationic protein with a pI of 11.35 and is capable of binding to heparin [20].

Regulatory relationships of XCL1

  • In addition, we have extended previous analyses of GPR5/XCR1 expression and show that this receptor is expressed in leukocyte cells previously shown to be responsive to lymphotactin [21].
  • Transcript destabilization can be ruled out as a mechanism by which CD28 down-regulates lymphotactin expression [22].

Other interactions of XCL1

  • CD3(+)CD8(+)CD5(-) cells also expressed higher levels of the XCL1 receptor; in addition, although not differing from CD3(+)CD8(+)CD5(+) cells in terms of the expression of most alpha- and beta-chemokines, they showed higher expression of CCL3/macrophage inflammatory protein-1alpha [16].
  • The levels of RANTES increased in LTNP and RP and the change of the levels after mitogen stimulation was statistically significant for both groups included [18].
  • There was an increased production of MIP 1-beta in 8/10 LTNP but only in 4/9 Progressors (Paired t-test/Wilcoxon Sign test, p-value < 0.05) [18].
  • NMR spectra of SDF-1alpha, RANTES, lymphotactin, and fractalkine indicate these chemokines adopt native structures [23].
  • In contrast to CD4(+) cells, Lptn exerted a potent costimulatory activity on CD8(+) T-cell proliferation and IL-2 secretion [2].

Analytical, diagnostic and therapeutic context of XCL1


  1. Identification of single C motif-1/lymphotactin receptor XCR1. Yoshida, T., Imai, T., Kakizaki, M., Nishimura, M., Takagi, S., Yoshie, O. J. Biol. Chem. (1998) [Pubmed]
  2. The C-class chemokine, lymphotactin, impairs the induction of Th1-type lymphokines in human CD4(+) T cells. Cerdan, C., Serfling, E., Olive, D. Blood (2000) [Pubmed]
  3. Glycosylated recombinant human XCL1/lymphotactin exhibits enhanced biologic activity. Dong, C., Chua, A., Ganguly, B., Krensky, A.M., Clayberger, C. J. Immunol. Methods (2005) [Pubmed]
  4. Anti-tumor responses induced by chemokine CCL19 transfected into an ovarian carcinoma model via fiber-mutant adenovirus vector. Gao, J.Q., Sugita, T., Kanagawa, N., Iida, K., Okada, N., Mizuguchi, H., Nakayama, T., Hayakawa, T., Yoshie, O., Tsutsumi, Y., Mayumi, T., Nakagawa, S. Biol. Pharm. Bull. (2005) [Pubmed]
  5. Adaptation to promiscuous usage of CC and CXC-chemokine coreceptors in vivo correlates with HIV-1 disease progression. Xiao, L., Rudolph, D.L., Owen, S.M., Spira, T.J., Lal, R.B. AIDS (1998) [Pubmed]
  6. Increased plasma interleukin-7 level correlates with decreased CD127 and Increased CD132 extracellular expression on T cell subsets in patients with HIV-1 infection. Sasson, S.C., Zaunders, J.J., Zanetti, G., King, E.M., Merlin, K.M., Smith, D.E., Stanley, K.K., Cooper, D.A., Kelleher, A.D. J. Infect. Dis. (2006) [Pubmed]
  7. New concepts in the immunopathogenesis of HIV infection. Pantaleo, G., Fauci, A.S. Annu. Rev. Immunol. (1995) [Pubmed]
  8. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Baum, M., Budzar, A.U., Cuzick, J., Forbes, J., Houghton, J.H., Klijn, J.G., Sahmoud, T. Lancet (2002) [Pubmed]
  9. Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors. Sankaran, S., Guadalupe, M., Reay, E., George, M.D., Flamm, J., Prindiville, T., Dandekar, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial. Fallowfield, L., Cella, D., Cuzick, J., Francis, S., Locker, G., Howell, A. J. Clin. Oncol. (2004) [Pubmed]
  11. HIV-1 strains from a cohort of American subjects reveal the presence of a V2 region extension unique to slow progressors and non-progressors. Wang, B., Spira, T.J., Owen, S., Lal, R.B., Saksena, N.K. AIDS (2000) [Pubmed]
  12. New developments in the treatment of postmenopausal breast cancer. Howell, A. Trends Endocrinol. Metab. (2005) [Pubmed]
  13. Aromatase inhibitors as adjuvant therapies in patients with breast cancer. Coombes, R.C., Gibson, L., Hall, E., Emson, M., Bliss, J. J. Steroid Biochem. Mol. Biol. (2003) [Pubmed]
  14. Constitutive expression of various chemokine genes in human T-cell lines infected with human T-cell leukemia virus type 1: role of the viral transactivator Tax. Baba, M., Imai, T., Yoshida, T., Yoshie, O. Int. J. Cancer (1996) [Pubmed]
  15. Expression of activation-induced, T cell-derived, and chemokine-related cytokine/lymphotactin and its functional role in rheumatoid arthritis. Blaschke, S., Middel, P., Dorner, B.G., Blaschke, V., Hummel, K.M., Kroczek, R.A., Reich, K., Benoehr, P., Koziolek, M., Müller, G.A. Arthritis Rheum. (2003) [Pubmed]
  16. CD8+ alpha beta+ T cells that lack surface CD5 antigen expression are a major lymphotactin (XCL1) source in peripheral blood lymphocytes. Stievano, L., Tosello, V., Marcato, N., Rosato, A., Sebelin, A., Chieco-Bianchi, L., Amadori, A. J. Immunol. (2003) [Pubmed]
  17. Migratory response of human natural killer cells to lymphotactin. Giancarlo, B., Silvano, S., Albert, Z., Mantovani, A., Allavena, P. Eur. J. Immunol. (1996) [Pubmed]
  18. CCR5 and beta-chemokines in HIV-1 infected children. Sanchez-Carrasquillo, E., García, V., Rivera, C.E., Febo, I., Melendez-Guerrero, L.M. Puerto Rico health sciences journal. (2000) [Pubmed]
  19. Differential chemokine expression profiles in human peripheral blood T lymphocytes: dependence on T-cell coreceptor and calcineurin signaling. Cristillo, A.D., Macri, M.J., Bierer, B.E. Blood (2003) [Pubmed]
  20. Purification, structural analysis, and function of natural ATAC, a cytokine secreted by CD8(+) T cells. Dorner, B., Müller, S., Entschladen, F., Schröder, J.M., Franke, P., Kraft, R., Friedl, P., Clark-Lewis, I., Kroczek, R.A. J. Biol. Chem. (1997) [Pubmed]
  21. Identification of viral macrophage inflammatory protein (vMIP)-II as a ligand for GPR5/XCR1. Shan, L., Qiao, X., Oldham, E., Catron, D., Kaminski, H., Lundell, D., Zlotnik, A., Gustafson, E., Hedrick, J.A. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  22. CD28 co-stimulation results in down-regulation of lymphotactin expression in human CD4(+) but not CD8(+) T cells via an IL-2-dependent mechanism. Olive, D., Cerdan, C. Eur. J. Immunol. (1999) [Pubmed]
  23. On-column refolding of recombinant chemokines for NMR studies and biological assays. Veldkamp, C.T., Peterson, F.C., Hayes, P.L., Mattmiller, J.E., Haugner, J.C., de la Cruz, N., Volkman, B.F. Protein Expr. Purif. (2007) [Pubmed]
  24. Lymphotactin gene-modified bone marrow dendritic cells act as more potent adjuvants for peptide delivery to induce specific antitumor immunity. Cao, X., Zhang, W., He, L., Xie, Z., Ma, S., Tao, Q., Yu, Y., Hamada, H., Wang, J. J. Immunol. (1998) [Pubmed]
  25. Identification and characterization of a glycosaminoglycan recognition element of the C chemokine lymphotactin. Peterson, F.C., Elgin, E.S., Nelson, T.J., Zhang, F., Hoeger, T.J., Linhardt, R.J., Volkman, B.F. J. Biol. Chem. (2004) [Pubmed]
  26. Chemical synthesis of lymphotactin: a glycosylated chemokine with a C-terminal mucin-like domain. Marcaurelle, L.A., Mizoue, L.S., Wilken, J., Oldham, L., Kent, S.B., Handel, T.M., Bertozzi, C.R. Chemistry (Weinheim an der Bergstrasse, Germany) (2001) [Pubmed]
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