Advertisement

ResearchIn-Press PreviewDermatologyImmunologyInflammation Open Access | 10.1172/jci.insight.200540

Keratinocyte VISTA attenuates UV light-induced skin injury by suppressing cutaneous type I interferon (IFN-I) response

Zachary T. Peters,1 Lindsay K. Mendyka,1 J'Voughnn A. Blake,1 Himanshu B. Goswami,1 Angelique N. Cortez,1 Grace E. Crossland,1 Sicong Shan,1 Elizabeth C. Nowak,1 Myana Keusch,1 Mrinal K. Sarkar,2 Johann E. Gudjonsson,2 Christopher M. Burns,3 Dorothea T. Barton,4 Bruce R. Blazar,5 Tyler J. Curiel,3 Rodwell Mabaera,3 Victoria P. Werth,6 Andrea Kalus,7 Keith B. Elkon,8 Randolph J. Noelle,1 and Sladjana Skopelja-Gardner1

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Peters, Z. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Mendyka, L. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Blake, J. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Goswami, H. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Cortez, A. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Crossland, G. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Shan, S. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Nowak, E. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Keusch, M. in: PubMed | Google Scholar |

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Sarkar, M. in: PubMed | Google Scholar |

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Gudjonsson, J. in: PubMed | Google Scholar |

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Burns, C. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Barton, D. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Blazar, B. in: PubMed | Google Scholar |

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Curiel, T. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Mabaera, R. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Werth, V. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Kalus, A. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Elkon, K. in: PubMed | Google Scholar |

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Noelle, R. in: PubMed | Google Scholar

1Department of Microbiology and Immunology, Dartmouth Geisel School of Medicine, Lebanon, United States of America

2Department of Dermatology, University of Michigan, Ann Arbor, United States of America

3Department of Medicine, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

4Department of Dermatology, Dartmouth Health, Dartmouth Hitchcock Medical Center, Lebanon, United States of America

5Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular , University of Minnesota, Minneapolis, United States of America

6Department of Dermatology, University of Pennsylvania and Corporal Michael J. Crescenz VAMC, Philadelphia, United States of America

7Division of Dermatology, University of Washington School of Medicine, Seattle, United States of America

8Division of Rheumatology, University of Washington School of Medicine, Seattle, United States of America

Find articles by Skopelja-Gardner, S. in: PubMed | Google Scholar |

Published October 6, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.200540.
Copyright © 2026, Peters et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 6, 2026 - Version history
View PDF
Abstract

Persistent production of type I interferons (IFN-Is) is a hallmark of cutaneous lupus erythematosus (CLE). Ultraviolet (UV) light stimulates IFN-I response in the skin and exacerbates CLE. Here, we identify V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) as a negative regulator of both basal and UV-induced IFN-I response in the skin and show that VISTA limits skin photosensitivity in an IFN-I-dependent manner, in part through Stimulator of Interferon Genes (STING). Furthermore, we demonstrate a novel role for VISTA in keratinocytes both at steady state and in response to UV light. Conditional deletion of VISTA in epidermal keratinocytes results in a ~10-fold increase in basal skin IFN-I scores and a heightened UV-induced skin injury score, both of which are dependent on IFN-I signaling. VISTA-targeting monoclonal antibodies suppress the UV-induced IFN-I response in human keratinocytes and in mice expressing human VISTA in vivo, thereby reducing UV-induced skin injury scores. Together, these findings identify VISTA as a keratinocyte-intrinsic checkpoint that restrains STING-associated IFN-I response in the skin and suggest VISTA agonism as a therapeutic strategy to limit photosensitivity in CLE.

Graphical Abstract
graphical abstract
Supplemental material

View Unedited blot and gel images

View Supplemental Tables

View

Version history
  • Version 1 (October 6, 2026): In-Press Preview
Advertisement
Advertisement