Absence of γ-chain in keratinocytes alters chemokine secretion resulting in reduced immune cell recruitment.

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Absence of γ-chain in keratinocytes alters chemokine secretion resulting in reduced immune cell recruitment.

J Invest Dermatol. 2017 Jun 17;:

Authors: Nowak K, Linzner D, Thrasher AJ, Lambert PF, Di WL, Burns SO

Abstract
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors. Following stimulation with the γc-ligand IL-15, γc-deficient keratinocytes demonstrate significantly impaired secretion of specific chemokines including CXCL1, CXCL8 and CCL20 resulting in reduced chemotaxis of dendritic cells and CD4+ T-cells. Furthermore, γc-deficient keratinocytes also exhibit defective induction of T-cell chemotaxis in a model of stable HPV18 infection. These findings suggest that persistent γc-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 novel treatment approaches.

PMID: 28634034 [PubMed - as supplied by publisher]

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