T Cells Control Chemokine Secretion by Keratinocytes

Tabea Rauschenberger

Viola Schmitt

Muhammad Azeem

Stefan Klein-Hessling

Matthias Klein+3 authors

Click here for additional data file.^{(112K, pdf)}

Click here for additional data file.^{(11M, PDF)}

^{Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Würzburg, Germany}

^{Comprehensive Cancer Center Mainfranken, Würzburg, Germany}

^{Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany}

^{Institute for Immunology, University Medical Center, University of Mainz, Mainz, Germany}

^{Research Center for Immunotherapy (FZI), University Medical Center, University of Mainz, Mainz, Germany}

^{Department of Immunology, University Cancer Center Mainz, University Medical Center, University of Mainz, Mainz, Germany}

Edited by: Ralf J. Ludwig, Universität zu Lübeck, Germany

Reviewed by: Carlo Chizzolini, Université de Genève, Switzerland; Mario Rotondi, University of Pavia, Italy

*Correspondence: Edgar Serfling ed.grubzreuw-inu.liam@e.gnilfres

Khalid Muhammad ed.grubzreuw-inu@dammahum.dilahk

This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology

Edited by: Ralf J. Ludwig, Universität zu Lübeck, Germany

Reviewed by: Carlo Chizzolini, Université de Genève, Switzerland; Mario Rotondi, University of Pavia, Italy

Received 2019 May 31; Accepted 2019 Jul 29.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8^{T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8}^{T cells. One key molecule is IFN-γ that is synthesized by CD8}^{T cells under the control of NFATc1 and NFATc2. CD8}^{T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8}^{T cells induced numerous type I IFN-inducible “defense genes” in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.}

Keywords: chemokine, keratinocytes, IFN, lichen planus, T cells, Nfatc1

Abstract

Acknowledgments

We are very much indebted to Doris Michel for excellent technical support. For mice we wish to thank Drs. M. Müller, A. Rao, and W. Birchmeier.

Acknowledgments

Glossary

Abbreviations

CsA	cyclosporine A
CTL	cytotoxic T cells
DKO T cells	T cells deficient for NFATc1 and NFATc2
Interferon-γ	IFN-γ
LP	lichen planus
NGS	next generation sequencing
TNF-α	Tumor necrosis factor α
T+I	TPA and ionomycin
IFN	Type I interferon.

Glossary

Footnotes

Funding. This work was supported by the Deutsche Forschungsgemeinschaft (DFG; SE469/24-1,GO811/5-1, KE1343/2-1), the Wilhelm Sander-Stiftung (ES and SK-H), and the IZKF Würzburg (Project A-371-KM, AK).

Footnotes

Click here for additional data file.^{(112K, pdf)}Click here for additional data file.^{(11M, PDF)}

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