Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1

Elisa Ruffo; Valeria Malacarne; Sasha E. Larsen; Rupali Das; Laura Patrussi; Christoph Wülfing; Christoph Biskup; Senta M. Kapnick; Katherine Verbist; Paige Tedrick; Pamela L. Schwartzberg; Cosima T. Baldari; Ignacio Rubio; Kim E. Nichols; Andrew L. Snow; Gianluca Baldanzi; Andrea Graziani

doi:10.1126/scitranslmed.aad1565

Research ArticleImmunodeficiency

Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1

Elisa Ruffo¹,*,
Valeria Malacarne¹,*,
Sasha E. Larsen²,*,
Rupali Das³,*,
Laura Patrussi⁴,
Christoph Wülfing⁵,
Christoph Biskup⁶,
Senta M. Kapnick⁷,
Katherine Verbist⁸,
Paige Tedrick⁸,
Pamela L. Schwartzberg⁷,
Cosima T. Baldari⁴,
Ignacio Rubio⁹,
Kim E. Nichols⁸,†,
Andrew L. Snow²,†,
Gianluca Baldanzi¹,† and
Andrea Graziani¹,¹⁰,†,‡

¹Department of Translational Medicine and Institute for Research and Cure of Autoimmune Diseases, University of Piemonte Orientale, 28100 Novara, Italy.
²Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
³Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
⁴Department of Life Sciences, University of Siena, 53100 Siena, Italy.
⁵School of Cellular and Molecular Medicine, University of Bristol, BS8 1TH Bristol, UK.
⁶Biomolecular Photonics Group, Jena University Hospital, D 07740 Jena, Germany.
⁷Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁸Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
⁹Integrated Research and Treatment Center, Center for Sepsis Control and Care and Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, D-07745 Jena, Germany.
¹⁰School of Medicine, University Vita e Salute San Raffaele, 20132 Milan, Italy.

↵‡Corresponding author. E-mail: graziani.andrea{at}hsr.it

↵* These authors contributed equally to this work.
↵† These authors contributed equally to this work.

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Science Translational Medicine 13 Jan 2016:
Vol. 8, Issue 321, pp. 321ra7
DOI: 10.1126/scitranslmed.aad1565

Elisa Ruffo

1Department of Translational Medicine and Institute for Research and Cure of Autoimmune Diseases, University of Piemonte Orientale, 28100 Novara, Italy.

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Valeria Malacarne

1Department of Translational Medicine and Institute for Research and Cure of Autoimmune Diseases, University of Piemonte Orientale, 28100 Novara, Italy.

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Sasha E. Larsen

2Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

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Rupali Das

3Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.

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Laura Patrussi

4Department of Life Sciences, University of Siena, 53100 Siena, Italy.

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Christoph Wülfing

5School of Cellular and Molecular Medicine, University of Bristol, BS8 1TH Bristol, UK.

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Christoph Biskup

6Biomolecular Photonics Group, Jena University Hospital, D 07740 Jena, Germany.

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Senta M. Kapnick

7Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Katherine Verbist

8Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.

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Paige Tedrick

8Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.

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Pamela L. Schwartzberg

7Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Cosima T. Baldari

4Department of Life Sciences, University of Siena, 53100 Siena, Italy.

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Ignacio Rubio

9Integrated Research and Treatment Center, Center for Sepsis Control and Care and Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, D-07745 Jena, Germany.

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Kim E. Nichols

8Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.

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Andrew L. Snow

2Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

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Gianluca Baldanzi

1Department of Translational Medicine and Institute for Research and Cure of Autoimmune Diseases, University of Piemonte Orientale, 28100 Novara, Italy.

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Andrea Graziani

1Department of Translational Medicine and Institute for Research and Cure of Autoimmune Diseases, University of Piemonte Orientale, 28100 Novara, Italy.

10School of Medicine, University Vita e Salute San Raffaele, 20132 Milan, Italy.

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For correspondence: graziani.andrea@hsr.it

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Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1

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