LY6S, 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 Ly6 family genes include eight genes that are flanked by the murine Ly6e and Ly6l genes and form an Ly6 subgroup referred to in this article as the Ly6a subfamily gene cluster. Ly6a , also known as Stem Cell Ag-1 and T cell–activating protein , is a member of the Ly6a subfamily gene cluster. No LY6 genes have been annotated within the syntenic LY6E to LY6L human locus. We report in this article on LY6S , a solitary human LY6 gene that is syntenic with the murine Ly6a subfamily gene cluster, and with which it shares a common ancestry. LY6S 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, LY6S , 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.

Primate-conserved Carbonic Anhydrase IV and murine-restricted Ly6c1 are new targets for crossing the blood-brain barrier

“…Nor did any Ly6-interacting AAV cross-react with the recently described human Ly6S, a close relative of murine Ly6a (Fig. 2g) (48) .…”

NK cells shape the clonal evolution of B cell leukaemia by IFN-γ production

“…There are several close orthologues of Ly6A in the human system. Besides a newly described human LY6A/Ly6S gene 30,31 , Ly6E and Ly6K have been well-described as close relatives in the human system. We compared the overall survival of ALL patients with a high versus low expression of LY6E and LY6K , respectively ( Figure 5H&I ).…”

“…The human orthologue for Ly6a has been under debate. Two independent groups recently suggested that the human orthologue LY6A/LY6S is located in region 8q24.3 of the human genome and is upregulated upon IFN-γ treatment and in pituitary tumours 55,56 .…”

“…The human orthologue for Ly6a has been under debate. Two independent groups recently suggested that the human orthologue LY6A / LY6S is located in region 8q24.3 of the human genome and is upregulated upon IFN-γ treatment and in pituitary tumours 55,56 . Interestingly, Hossiny et al showed that LY6E and LY6K, which had been discussed previously as the human orthologues of Ly6a , promote breast cancer in vivo and drive drug sensitivity and epithelial-to-mesenchymal transition (EMT).…”

Primate-conserved carbonic anhydrase IV and murine-restricted LY6C1 enable blood-brain barrier crossing by engineered viral vectors

“…S2C) nor did any LY6-interacting AAV cross-react with the recently described human LY6S, a close relative of murine LY6A (Fig. 2G) (50). While we used validated candidate receptor clones (table S1), it is possible that lack of membrane expression could result in a false negative in our screens.…”