<i>LY6S,</i> a New IFN-Inducible Human Member of the Ly6a Subfamily Expressed by Spleen Cells and Associated with Inflammation and Viral Resistance

Abstract

Syntenic genomic loci on human chromosome 8 and mouse chromosome 15 (mChr15) code for LY6/Ly6 (lymphocyte Ag 6) family proteins. The 23 murine <i>Ly6</i> family genes include eight genes that are flanked by the murine <i>Ly6e</i> and <i>Ly6l</i> genes and form an Ly6 subgroup referred to in this article as the Ly6a subfamily gene cluster. <i>Ly6a</i>, also known as <i>Stem Cell Ag-1</i> and <i>T cell-activating protein</i>, is a member of the Ly6a subfamily gene cluster. No <i>LY6</i> genes have been annotated within the syntenic <i>LY6E</i> to <i>LY6L</i> human locus. We report in this article on <i>LY6S</i>, a solitary human <i>LY6</i> gene that is syntenic with the murine Ly6a subfamily gene cluster, and with which it shares a common ancestry. <i>LY6S</i> codes for the IFN-inducible GPI-linked LY6S-iso1 protein that contains only 9 of the 10 consensus LY6 cysteine residues and is most highly expressed in a nonclassical spleen cell population. Its expression leads to distinct shifts in patterns of gene expression, particularly of genes coding for inflammatory and immune response proteins, and LY6S-iso1-expressing cells show increased resistance to viral infection. Our findings reveal the presence of a previously unannotated human IFN-stimulated gene, <i>LY6S</i>, which has a 1:8 ortholog relationship with the genes of the Ly6a subfamily gene cluster, is most highly expressed in spleen cells of a nonclassical cell lineage, and whose expression induces viral resistance and is associated with an inflammatory phenotype and with the activation of genes that regulate immune responses.