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Absence of γ-Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2017 Oct; Vol. 137 (10), pp. 2120-2130. Date of Electronic Publication: 2017 Jun 17. - Publication Year :
- 2017
-
Abstract
- Loss-of-function mutations in the common gamma (γc) 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 γc-deficiency in other cell types. Here we show that keratinocytes, the only cell type directly infected by human papilloma virus, express functional γc and its co-receptors. After stimulation with the γc-ligand IL-15, γc-deficient keratinocytes show significantly impaired secretion of specific chemokines including CXCL1, CXCL8, and CCL20, resulting in reduced chemotaxis of dendritic cells and CD4 <superscript>+</superscript> T cells. Furthermore, γc-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 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 different treatment approaches.<br /> (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line
Cell Movement
Chemokines biosynthesis
Flow Cytometry
Heavy Chain Disease genetics
Heavy Chain Disease metabolism
Humans
Keratinocytes immunology
Keratinocytes pathology
RNA genetics
Reverse Transcriptase Polymerase Chain Reaction
Chemokines genetics
Gene Expression Regulation
Heavy Chain Disease immunology
Immunity, Innate
Immunoglobulin gamma-Chains metabolism
Keratinocytes metabolism
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 137
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 28634034
- Full Text :
- https://doi.org/10.1016/j.jid.2017.05.024