NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells-Reference-Cited by-同舟云学术

NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells

Published:2020-05-26 Issue:8 Volume:217 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Babic Marina¹²^ORCID,Dimitropoulos Christoforos¹,Hammer Quirin¹^ORCID,Stehle Christina¹^ORCID,Heinrich Frederik³^ORCID,Sarsenbayeva Assel¹,Eisele Almut¹,Durek Pawel⁴,Mashreghi Mir-Farzin³^ORCID,Lisnic Berislav⁵⁶,Van Snick Jacques⁷,Löhning Max⁸⁹^ORCID,Fillatreau Simon¹⁰^ORCID,Withers David R.¹¹^ORCID,Gagliani Nicola¹²,Huber Samuel¹²,Flavell Richard A.¹³¹⁴^ORCID,Polic Bojan⁶^ORCID,Romagnani Chiara¹²^ORCID

Affiliation:

1. Innate Immunity, German Rheumatism Research Centre—a Leibniz Institute, Berlin, Germany

2. Division of Gastroenterology, Infectiology and Rheumatology, Medical Department I, Charité-Universitätsmedizin Berlin, Berlin, Germany

3. Therapeutic Gene Regulation, German Rheumatism Research Centre—a Leibniz Institute, Berlin, Germany

4. Cell Biology, German Rheumatism Research Centre—a Leibniz Institute, Berlin, Germany

5. Center for Proteomics, University of Rijeka, Rijeka, Croatia

6. Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Croatia

7. Ludwig Institute for Cancer Research, Brussels, Belgium

8. Pitzer Laboratory of Osteoarthritis Research, German Rheumatism Research Centre—a Leibniz Institute, Berlin, Germany

9. Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany

10. Institut Necker-Enfants Malades, INSERM U1151/CNRS UMR8253, Faculté de Médecine Paris Descartes, Paris, France

11. Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

12. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

13. Department of Immunobiology, Yale University School of Medicine, New Haven, CT

14. Howard Hughes Medical Institute, Yale University, New Haven, CT

Abstract

NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes. Despite its established role as a potent activator of the immune system, NKG2D-driven regulation of CD4+ T helper (Th) cell–mediated immunity remains unclear. In this study, we demonstrate that NKG2D modulates Th1 and proinflammatory T-bet+ Th17 cell effector functions in vitro and in vivo. In particular, NKG2D promotes higher production of proinflammatory cytokines by Th1 and T-bet+ Th17 cells and reinforces their transcription of type 1 signature genes, including Tbx21. Conditional deletion of NKG2D in T cells impairs the ability of antigen-specific CD4+ T cells to promote inflammation in vivo during antigen-induced arthritis and experimental autoimmune encephalomyelitis, indicating that NKG2D is an important target for the amelioration of Th1- and Th17-mediated chronic inflammatory diseases.

Funder

European Union

Seventh Framework Programme

Marie Curie Intra-European Fellowship

Deutsche Forschungsgemeinschaft

State of Berlin

European Regional Development Fund

Croatian Science Foundation

Leibniz ScienceCampus Chronic Inflammation

Publisher

Rockefeller University Press

Subject