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

作者：Nowak Karolin; Linzner Daniela; Thrasher Adrian J; Lambert Paul F; Di Wei Li; Burns Siobhan O

来源：Journal of Investigative Dermatology, 2017, 137(10): 2120-2130.

DOI：10.1016/j.jid.2017.05.024

Loss-of-function mutations in the common gamma (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 gamma c-deficiency in other cell types. Here we show that keratinocytes, the only cell type directly infected by human papilloma virus, express functional gamma c and its co-receptors. After stimulation with the gamma c-ligand IL-15, gamma 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, gamma 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 gamma 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.

• 出版日期2017-10