title: Phosphatase and tensin homolog (PTEN) in antigen-presenting cells controls Th17-mediated autoimmune arthritis.
abstract: BACKGROUND
  Autoreactive T cells are a central element in many systemic autoimmune diseases. The generation of these pathogenic T cells is instructed by antigen-presenting cells (APCs). However, signaling pathways in APCs that drive autoimmune diseases, such as rheumatoid arthritis, are not understood.
  
  
  METHODS
  We measured phenotypic maturation, cytokine production and induction of T cell proliferation of APCs derived from wt mice and mice with a myeloid-specific deletion of PTEN (myeloid PTEN(-/-)) in vitro and in vivo. We induced collagen-induced arthritis (CIA) and K/BxN serum transfer arthritis in wt and myeloid-specific PTEN(-/-) mice. We measured the cellular composition of lymph nodes by flow cytometry and cytokines in serum and after ex vivo stimulation of T cells.
  
  
  RESULTS
  We show that myeloid-specific PTEN(-/-) mice are almost protected from CIA. Myeloid-specific deletion of PTEN leads to a significant reduction of cytokine expression pivotal for the induction of systemic autoimmunity such as interleukin (IL)-23 and IL-6, leading to a significant reduction of a Th17 type of immune response characterized by reduced production of IL-17 and IL-22. In contrast, myeloid-specific PTEN deficiency did not affect K/BxN serum transfer arthritis, which is independent of the adaptive immune system and solely depends on innate effector functions.
  
  
  CONCLUSIONS
  These data demonstrate that the presence of PTEN in myeloid cells is required for the development of CIA. Deletion of PTEN in myeloid cells inhibits the development of autoimmune arthritis by preventing the generation of a pathogenic Th17 type of immune response.
authors: Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. stephan.blueml@meduniwien.ac.at.
authors: Stephan
authors: S
authors: Blüml
authors: Institute for Physiology, Center for Physiology and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, A-1090, Vienna, Austria. emine.sahin@meduniwien.ac.at.
authors: Emine
authors: E
authors: Sahin
authors: Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. victoria.saferding@meduniwien.ac.at.
authors: Victoria
authors: V
authors: Saferding
authors: Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. eliana.gocalvesalves@meduniwien.ac.at.
authors: Eliana
authors: E
authors: Goncalves-Alves
authors: Institute for Physiology, Center for Physiology and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, A-1090, Vienna, Austria. eva.hainzl@vetmeduni.ac.at.
authors: Eva
authors: E
authors: Hainzl
authors: Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. birgit.niederreiter@meduniwien.ac.at.
authors: Birgit
authors: B
authors: Niederreiter
authors: Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. anastasia.hladik@meduniwien.ac.at.
authors: Anastasia
authors: A
authors: Hladik
authors: Institute for Physiology, Center for Physiology and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, A-1090, Vienna, Austria. Tobias.lohmeyer@gmx.com.
authors: Tobias
authors: T
authors: Lohmeyer
authors: Institute for Physiology, Center for Physiology and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, A-1090, Vienna, Austria. julia.brunner@meduniwien.ac.at.
authors: Julia S
authors: JS
authors: Brunner
authors: Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. michael.bonelli@meduniwien.ac.at.
authors: Michael
authors: M
authors: Bonelli
authors: Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Center, Geert Grooteplein-Zuid 10, 6525, GA, Nijmegen, The Netherlands. m.koenders@reuma.umcn.nl.
authors: Marije I
authors: MI
authors: Koenders
authors: Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Center, Geert Grooteplein-Zuid 10, 6525, GA, Nijmegen, The Netherlands. W.vandenBerg@reuma.umcn.nl.
authors: Wim B
authors: WB
authors: van den Berg
authors: CeMM - Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, Vienna, 1090, Austria. GSuperti-Furga@cemm.oeaw.ac.at.
authors: Giulio
authors: G
authors: Superti-Furga
authors: Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. josef.smolen@wienkav.at.
authors: Josef S
authors: JS
authors: Smolen
authors: Institute for Physiology, Center for Physiology and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, A-1090, Vienna, Austria. gernot.schabbauer@meduniwien.ac.at.
authors: Gernot
authors: G
authors: Schabbauer
authors: Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. kurt.redlich@meduniwien.ac.at.
authors: Kurt
authors: K
authors: Redlich
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse