Absence of ?-Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment.

ABSTRACT: Loss-of-function mutations in the common gamma (?c) chain cytokine receptor subunit give rise to severe combined immunodeficiency characterized by lack of T and natural killer cells and infant death from infection. Hematopoietic stem cell transplantation or gene therapy offer a cure, but despite successful replacement of lymphoid immune lineages, a long-term risk of severe cutaneous human papilloma virus infections persists, possibly related to persistent ?c-deficiency in other cell types. Here we show that keratinocytes, the only cell type directly infected by human papilloma virus, express functional ?c and its co-receptors. After stimulation with the ?c-ligand IL-15, ?c-deficient keratinocytes show significantly impaired secretion of specific chemokines including CXCL1, CXCL8, and CCL20, resulting in reduced chemotaxis of dendritic cells and CD4+ T cells. Furthermore, ?c-deficient keratinocytes also exhibit defective induction of T-cell chemotaxis in a model of stable human papilloma virus-18 infection. These findings suggest that persistent ?c-deficiency in keratinocytes alters immune cell recruitment to the skin, which may contribute to the development and persistence of warts in this condition and would require different treatment approaches.

SUBMITTER: Nowak K 

PROVIDER: S-EPMC5896775 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature