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

• Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial [10].
• Increasing quasispecies diversity in HIV-1 strains, over time, abrogation of a V3 region N-linked glycosylation site in > 60% of the clones, and, importantly, an extended V2 region were unique features of HIV-1 strains from SP and LTNP [11].
• The final results of the "Arimidex", Tamoxifen, Alone or in Combination (ATAC) trial, at a median follow-up of more than five years, and recent results from switching studies with anastrozole and exemestane, strengthen the position of these AIs as adjuvant treatment for hormone receptor-positive early breast cancer [12].
• Early studies indicated that aminoglutethimide/hydrocortisone could benefit postmenopausal patients with primary breast cancer, and in 2001, the ATAC study showed that the third generation aromatase inhibitor, anastrozole, seemed superior to tamoxifen in that anastrozole-treated patients had a longer disease-free survival [13].

Biological context of XCL1

• In humans, there are two highly homologous SCM-1 genes encoding SCM-1alpha and SCM-1beta with two amino acid substitutions [1].
• Induction of tax in JPX-9 with Cd2+ was accompanied by rapid induction of IL-8, IP-10, MIP-1alpha, MIP-1beta, 1309 and SCM-1 as determined by reverse transcription PCR [14].
• Transfections in Jurkat cells showed a Lptn-mediated transcriptional down-regulation of gene-promoter activities specific for Th1-type lymphokines, as well as of nuclear factor of activated T cells (NF-AT) but not AP-1 or NF-KB enhancer activities [2].
• The phenotype of peripheral blood mononuclear cells (PBMCs) expressing ATAC/Lptn was analyzed by intracellular cytokine staining and flow cytometry [15].
• In vitro, ATAC/Lptn stimulation of FLS resulted in a marked down-regulation of matrix metalloproteinase 2 production [15].

Anatomical context of XCL1

• XCL1 expression was mostly confined to a CD3(+)CD8(+) subset not expressing CD5, where XCL1 expression equaled that shown by gammadelta(+) T cells [16].
• In vitro activation was associated with a substantial increase in XCL1 expression in both PBMC and CD8(+) cells, but not in CD4(+) lymphocytes [16].
• METHODS: ATAC/Lptn levels in serum and synovial fluid samples were measured by sandwich enzyme-linked immunosorbent assay [15].
• CONCLUSION: These data indicate that in RA synovium, ATAC/Lptn is mainly produced by T cells [15].
• Migratory response of human natural killer cells to lymphotactin [17].

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

• The preferential expression of XCL1 in CD8(+) cells was confirmed by measuring XCL1 production in culture supernatants, and a good correlation was found between figures obtained by real-time PCR and XCL1 contents [16].
• Expression of messenger RNA for ATAC/Lptn in synovial tissues was analyzed by reverse transcription-polymerase chain reaction (PCR) and by in situ hybridization, and was quantitated by real-time PCR [15].
• Lptn expression of Lptn-DC was further confirmed by RT-PCR [24].
• Substitutions in and around this binding site and surface plasmon resonance analysis of heparin binding affinity identified two arginine residues of lymphotactin as critical for glycosaminoglycan binding [25].
• The synthesis of a 93-residue chemokine, lymphotactin, containing eight sites of O-linked glycosylation, was achieved using the technique of native chemical ligation [26].

References