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Gene Review

Xcl1  -  chemokine (C motif) ligand 1

Mus musculus

Synonyms: AI661682, ATAC, C motif chemokine 1, Cytokine SCM-1, LTN, ...
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Disease relevance of Xcl1

  • Upregulation of CD80 and CD54 on murine CT26 colon carcinoma cells was observed after combined transfection with adenovirus encoding CD (AdCD) and adenovirus encoding murine Ltn (AdLtn) followed by administration of 5-fluorocytosine (5FC) in vitro [1].
  • In the murine model with the pre-established subcutaneous B16 melanoma, immunization with Lptn/gp100-DC inhibited the tumor growth most significantly when compared with other counterparts [2].
  • This difference in disease progression occurs despite the fact that E-55+ MuLV causes persistent infection in both immunocompetent BALB/c-H-2(k) (BALB.K) progressor (P) and C57BL/10-H-2(k) (B10.BR) long-term nonprogressor (LTNP) mice [3].
  • In contrast to immunocompetent mice, immunosuppressed mice from both P and LTNP strains develop lymphomas about 2 months after infection, indicating that the LTNP phenotype is determined by the immune response of the infected mouse [3].
  • Adenoviral vectors expressing lymphotactin and interleukin 2 or lymphotactin and interleukin 12 synergize to facilitate tumor regression in murine breast cancer models [4].

High impact information on Xcl1

  • Coexpression of the T-cell growth factor interleukin-2, however, greatly expanded the T lymphocytes attracted by Lptn, affording protection from the growth of established tumor in a CD4+ and CD8+ T cell-dependent manner [5].
  • Lymphotactin is similar to members of both the Cys-Cys and Cys-X-Cys chemokine families but lacks two of the four cysteine residues that are characteristic of the chemokines [6].
  • The gene encoding lymphotactin maps to chromosome one [6].
  • During screening of a complementary DNA library generated from activated mouse pro-T cells, a cytokine designated lymphotactin was discovered [6].
  • We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-alpha- (a proinflammatory cytokine) stimulated leukocyte infiltration [7].

Chemical compound and disease context of Xcl1


Biological context of Xcl1


Anatomical context of Xcl1

  • Ltn is thus expressed in mast cells and may contribute to the recruitment of lymphocytes to areas of allergic inflammation [13].
  • Using the reverse transcriptase-PCR and Northern blot analysis, we found that the Ltn gene is inducible in C1.MC/C57.1 and murine bone marrow-cultured mast cells (BMCMC) by Fc(epsilon)RI aggregation [13].
  • Activation of a human mast cell (HMC-1) or basophil cell line (KU812) similarly led to transcription of Ltn [13].
  • Taken together, our data provide solid evidence of a potent synergy between adoptive CD4+ and CD8+ T-cell therapy and Lptn gene transfer into tumor tissues, which culminated in the eradication of well-established tumor masses [10].
  • We have shown that transplanted SP2/0 myeloma tumors that have been engineered to express lymphotactin (Lptn) invariably regress under the influence of infiltrating XCR1+T cells and neutrophils [10].

Associations of Xcl1 with chemical compounds

  • Fc(epsilon)RI aggregation-dependent Ltn mRNA expression was detected by 1 to 2 h, maximal at 6 h, independent of de novo protein synthesis, and was inhibited by cyclosporin A and dexamethasone [13].
  • Adenovirus-mediated lymphotactin gene transfer improves therapeutic efficacy of cytosine deaminase suicide gene therapy in established murine colon carcinoma [1].
  • Clinical findings with the nonsteroidal inhibitor anastrozole in combination with tamoxifen (ATAC trial) were consistent with our results [14].
  • AIs are currently under evaluation in the adjuvant setting, and preliminary results of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial have been reported [15].

Regulatory relationships of Xcl1


Other interactions of Xcl1

  • Although GM+ mice are able to express the chemokine RANTES, they lack the ability to express other inflammatory chemokines such as lymphotactin and MIP-1beta [16].
  • After stimulation with SP2/0 cells, these T cells were CD25+FasL+L-selectin-, expressed XCR-1, and were chemoattracted by Lptn in vitro [10].
  • Both RANTES and IP-10 gene transcripts were first detected in these LG when the mice were 8 weeks of age and amounts increased markedly during the course of active disease; lymphotactin mRNA was also expressed but at lower levels [17].
  • At this time point messages encoding lymphotactin (Ltn) and metallothionein were also increased [18].
  • In this study, Lptn and/or melanoma-associated antigen gp100 were transfected into mouse bone marrow-derived DC, which were used as vaccines in B16 melanoma model [2].

Analytical, diagnostic and therapeutic context of Xcl1


  1. Adenovirus-mediated lymphotactin gene transfer improves therapeutic efficacy of cytosine deaminase suicide gene therapy in established murine colon carcinoma. Ju, D.W., Tao, Q., Cheng, D.S., Zhang, W., Zhang, M., Hamada, H., Cao, X. Gene Ther. (2000) [Pubmed]
  2. Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100. Xia, D.J., Zhang, W.P., Zheng, S., Wang, J., Pan, J.P., Wang, Q., Zhang, L.H., Hamada, H., Cao, X. Gene Ther. (2002) [Pubmed]
  3. Genetic regulation of long-term nonprogression in E-55+ murine leukemia virus infection in mice. Panoutsakopoulou, V., Hunter, K., Sieck, T.G., Blankenhorn, E.P., Blank, K.J. J. Virol. (1999) [Pubmed]
  4. Adenoviral vectors expressing lymphotactin and interleukin 2 or lymphotactin and interleukin 12 synergize to facilitate tumor regression in murine breast cancer models. Emtage, P.C., Wan, Y., Hitt, M., Graham, F.L., Muller, W.J., Zlotnik, A., Gauldie, J. Hum. Gene Ther. (1999) [Pubmed]
  5. Combined chemokine and cytokine gene transfer enhances antitumor immunity. Dilloo, D., Bacon, K., Holden, W., Zhong, W., Burdach, S., Zlotnik, A., Brenner, M. Nat. Med. (1996) [Pubmed]
  6. Lymphotactin: a cytokine that represents a new class of chemokine. Kelner, G.S., Kennedy, J., Bacon, K.B., Kleyensteuber, S., Largaespada, D.A., Jenkins, N.A., Copeland, N.G., Bazan, J.F., Moore, K.W., Schall, T.J. Science (1994) [Pubmed]
  7. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation. Viswanathan, K., Dhabhar, F.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Lymphotactin enhances the in-vitro immune efficacy of dendritoma formed by dendritic cells and mouse hepatocellular carcinoma cells. Zhang, H., Jiang, G.P., Zheng, S.S., Wu, L.H., Zhu, F., Yang, Z.L. J. Zhejiang Univ. Sci. (2004) [Pubmed]
  9. MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines. Dorner, B.G., Scheffold, A., Rolph, M.S., Huser, M.B., Kaufmann, S.H., Radbruch, A., Flesch, I.E., Kroczek, R.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  10. Synergistic enhancement of antitumor immunity with adoptively transferred tumor-specific CD4+ and CD8+ T cells and intratumoral lymphotactin transgene expression. Huang, H., Li, F., Gordon, J.R., Xiang, J. Cancer Res. (2002) [Pubmed]
  11. Lymphotactin acts as an innate mucosal adjuvant. Lillard, J.W., Boyaka, P.N., Hedrick, J.A., Zlotnik, A., McGhee, J.R. J. Immunol. (1999) [Pubmed]
  12. Differential chemokine gene expression in corneal transplant rejection. Yamagami, S., Miyazaki, D., Ono, S.J., Dana, M.R. Invest. Ophthalmol. Vis. Sci. (1999) [Pubmed]
  13. Lymphotactin gene expression in mast cells following Fc(epsilon) receptor I aggregation: modulation by TGF-beta, IL-4, dexamethasone, and cyclosporin A. Rumsaeng, V., Vliagoftis, H., Oh, C.K., Metcalfe, D.D. J. Immunol. (1997) [Pubmed]
  14. Therapeutic observations in MCF-7 aromatase xenografts. Brodie, A., Jelovac, D., Macedo, L., Sabnis, G., Tilghman, S., Goloubeva, O. Clin. Cancer Res. (2005) [Pubmed]
  15. Challenges in the endocrine management of breast cancer. Mouridsen, H.T., Rose, C., Brodie, A.H., Smith, I.E. Breast (Edinburgh, Scotland) (2003) [Pubmed]
  16. Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection. Gonzalez-Juarrero, M., Hattle, J.M., Izzo, A., Junqueira-Kipnis, A.P., Shim, T.S., Trapnell, B.C., Cooper, A.M., Orme, I.M. J. Leukoc. Biol. (2005) [Pubmed]
  17. T cell attractant chemokine expression initiates lacrimal gland destruction in nonobese diabetic mice. Törnwall, J., Lane, T.E., Fox, R.I., Fox, H.S. Lab. Invest. (1999) [Pubmed]
  18. Inflammatory and antioxidant gene expression in C57BL/6J mice after lethal and sublethal ozone exposures. Johnston, C.J., Stripp, B.R., Reynolds, S.D., Avissar, N.E., Reed, C.K., Finkelstein, J.N. Exp. Lung Res. (1999) [Pubmed]
  19. Lymphotactin is produced by NK cells and attracts both NK cells and T cells in vivo. Hedrick, J.A., Saylor, V., Figueroa, D., Mizoue, L., Xu, Y., Menon, S., Abrams, J., Handel, T., Zlotnik, A. J. Immunol. (1997) [Pubmed]
  20. Chemokine expression by intraepithelial gamma delta T cells. Implications for the recruitment of inflammatory cells to damaged epithelia. Boismenu, R., Feng, L., Xia, Y.Y., Chang, J.C., Havran, W.L. J. Immunol. (1996) [Pubmed]
  21. Early and late chemokine production correlates with cellular recruitment in cardiac allograft vasculopathy. Yun, J.J., Fischbein, M.P., Laks, H., Fishbein, M.C., Espejo, M.L., Ebrahimi, K., Irie, Y., Berliner, J., Ardehali, A. Transplantation (2000) [Pubmed]
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