A protective Langerhans cell–keratinocyte axis that is dysfunctional in photosensitivity

William D. Shipman; Susan Chyou; Anusha Ramanathan; Peter M. Izmirly; Sneh Sharma; Tania Pannellini; Dragos C. Dasoveanu; Xiaoping Qing; Cynthia M. Magro; Richard D. Granstein; Michelle A. Lowes; Eric G. Pamer; Daniel H. Kaplan; Jane E. Salmon; Babak J. Mehrara; James W. Young; Robert M. Clancy; Carl P. Blobel; Theresa T. Lu

doi:10.1126/scitranslmed.aap9527

Research ArticleSKIN

A protective Langerhans cell–keratinocyte axis that is dysfunctional in photosensitivity

View ORCID ProfileWilliam D. Shipman ¹,²,³,
View ORCID ProfileSusan Chyou³,
Anusha Ramanathan³,
Peter M. Izmirly⁴,
Sneh Sharma⁵,⁶,
Tania Pannellini³,
Dragos C. Dasoveanu³,⁷,
Xiaoping Qing³,
Cynthia M. Magro⁸,
View ORCID ProfileRichard D. Granstein⁹,
Michelle A. Lowes¹⁰,
View ORCID ProfileEric G. Pamer⁶,
View ORCID ProfileDaniel H. Kaplan¹¹,¹²,
View ORCID ProfileJane E. Salmon²,³,¹³,¹⁴,
Babak J. Mehrara¹⁵,
View ORCID ProfileJames W. Young⁵,⁶,¹⁰,¹³,¹⁶,
Robert M. Clancy⁴,
Carl P. Blobel⁷,¹³,¹⁷,¹⁸ and
View ORCID ProfileTheresa T. Lu ²,³,¹⁴,¹⁹,*

¹Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY 10065, USA.
²Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
³Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.
⁴Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
⁵Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁶Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁷Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY 10065, USA.
⁸Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
⁹Department of Dermatology, Weill Cornell Medicine, New York, NY 10065, USA.
¹⁰Rockefeller University, New York, NY 10065, USA.
¹¹Department of Dermatology, University of Pittsburgh, PA 15260, USA.
¹²Department of Immunology, University of Pittsburgh, PA 15260, USA.
¹³Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
¹⁴Division of Rheumatology and Pediatric Rheumatology, Hospital for Special Surgery, New York, NY 10021, USA.
¹⁵Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
¹⁶Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
¹⁷Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA.
¹⁸Institute for Advanced Studies, Technical University Munich, Munich, Germany.
¹⁹Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.

↵*Corresponding author. Email: lut{at}hss.edu

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Science Translational Medicine 15 Aug 2018:
Vol. 10, Issue 454, eaap9527
DOI: 10.1126/scitranslmed.aap9527

William D. Shipman

1Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY 10065, USA.

2Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.

3Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.

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Susan Chyou

3Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.

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Anusha Ramanathan

3Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.

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Peter M. Izmirly

4Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.

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Sneh Sharma

5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

6Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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Tania Pannellini

3Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.

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Dragos C. Dasoveanu

3Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.

7Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY 10065, USA.

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Xiaoping Qing

3Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.

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Cynthia M. Magro

8Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.

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Richard D. Granstein

9Department of Dermatology, Weill Cornell Medicine, New York, NY 10065, USA.

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Michelle A. Lowes

10Rockefeller University, New York, NY 10065, USA.

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Eric G. Pamer

6Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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Daniel H. Kaplan

11Department of Dermatology, University of Pittsburgh, PA 15260, USA.

12Department of Immunology, University of Pittsburgh, PA 15260, USA.

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Jane E. Salmon

2Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.

3Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.

13Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.

14Division of Rheumatology and Pediatric Rheumatology, Hospital for Special Surgery, New York, NY 10021, USA.

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Babak J. Mehrara

15Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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James W. Young

5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

6Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

10Rockefeller University, New York, NY 10065, USA.

13Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.

16Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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Robert M. Clancy

4Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.

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Carl P. Blobel

7Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY 10065, USA.

13Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.

17Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA.

18Institute for Advanced Studies, Technical University Munich, Munich, Germany.

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Theresa T. Lu

2Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.

3Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021, USA.

14Division of Rheumatology and Pediatric Rheumatology, Hospital for Special Surgery, New York, NY 10021, USA.

19Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.

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For correspondence: lut@hss.edu

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Langerhans cells limit ultraviolet radiation–induced keratinocyte apoptosis and skin injury, and this axis is dysfunctional in lupus photosensitivity.

A protective Langerhans cell–keratinocyte axis that is dysfunctional in photosensitivity

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