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

Nowak, K; Linzner, D; Thrasher, AJ; Lambert, PF; Di, WL; Burns, SO; (2017) Absence of γ-chain in keratinocytes alters chemokine secretion resulting in reduced immune cell recruitment. Journal of Investigative Dermatology , 137 (10) pp. 2120-2130. 10.1016/j.jid.2017.05.024. Green open access

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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.

Type: Article
Title: Absence of γ-chain in keratinocytes alters chemokine secretion resulting in reduced immune cell recruitment
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jid.2017.05.024
Publisher version: http://dx.doi.org/10.1016/j.jid.2017.05.024
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Human papillomavirus, Primary Immunodeficiency, X-SCID, common γ-chain
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1561074
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