Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome

Author:

Völkl Simon1,Rensing-Ehl Anne2,Allgäuer Andrea1,Schreiner Elisabeth1,Lorenz Myriam Ricarda3,Rohr Jan24,Klemann Christian24,Fuchs Ilka2,Schuster Volker5,von Bueren André O.6,Naumann-Bartsch Nora7,Gambineri Eleonora8,Siepermann Kathrin9,Kobbe Robin10,Nathrath Michaela1112,Arkwright Peter D.13,Miano Maurizio14,Stachel Klaus-Daniel7,Metzler Markus7,Schwarz Klaus234,Kremer Anita N.1,Speckmann Carsten215,Ehl Stephan215,Mackensen Andreas1

Affiliation:

1. Department of Internal Medicine 5, Haematology and Oncology, University Hospital Erlangen, Erlanger, Germany;

2. Center for Chronic Immunodeficiency, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany;

3. Institute for Transfusion Medicine, University of Ulm, Ulm, Germany;

4. Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service, Ulm, Germany;

5. Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany;

6. Division of Pediatric Haematology and Oncology, Department of Pediatric and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany;

7. Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany;

8. Department of Neuroscience, Psychology, Drug Area and Child Health (NEUROFARBA), Section of Child's Health, University of Florence, Florence, Italy;

9. Department of Pediatric and Adolescent Medicine, HELIOS Klinikum Krefeld, Krefeld, Germany;

10. Department of Pediatrics, University Medical Centre Hamburg, Hamburg, Germany;

11. Department of Pediatric Oncology, Klinikum Kassel, Kassel, Germany;

12. Department of Pediatrics, Pediatric Oncology Center, Technische Universität München, Munich, Germany;

13. Department of Pediatric Allergy and Immunology, Royal Manchester Children’s Hospital, University of Manchester, Manchester, United Kingdom;

14. Clinical and Experimental Haematology Unit, Giannina Gaslini Children’s Hospital, Genoa, Italy; and

15. Center for Paediatrics and Adolescent Medicine, University Medical Center, University of Freiburg, Freiburg, Germany

Abstract

Key Points ALPS DNT cells and their putative precursors reveal high proliferative activity in vivo, which is associated with hyperactive mTOR signaling. Rapamycin therapy controls mitotic activity and abnormal differentiation of ALPS DNT cells and reduces CD4+ or CD8+ precursor DNT cells.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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