Glucocorticoid receptor in stromal cells is essential for glucocorticoid-mediated suppression of inflammation in arthritis

Annals of the Rheumatic Diseases
Mascha KoenenJan P Tuckermann

Abstract

Glucocorticoid (GC) therapy is frequently used to treat rheumatoid arthritis due to potent anti-inflammatory actions of GCs. Direct actions of GCs on immune cells were suggested to suppress inflammation. Define the role of the glucocorticoid receptor (GR) in stromal cells for suppression of inflammatory arthritis. Bone marrow chimeric mice lacking the GR in the hematopoietic or stromal compartment, respectively, and mice with impaired GR dimerisation (GRdim) were analysed for their response to dexamethasone (DEX, 1 mg/kg) treatment in serum transfer-induced arthritis (STIA). Joint swelling, cell infiltration (histology), cytokines, cell composition (flow cytometry) and gene expression were analysed and RNASeq of wild type and GRdim primary murine fibroblast-like synoviocytes (FLS) was performed. GR deficiency in immune cells did not impair GC-mediated suppression of STIA. In contrast, mice with GR-deficient or GR dimerisation-impaired stromal cells were resistant to GC treatment, despite efficient suppression of cytokines. Intriguingly, in mice with impaired GR function in the stromal compartment, GCs failed to stimulate non-classical, non-activated macrophages (Ly6Cneg, MHCIIneg) and associated anti-inflammatory markers CD163,...Continue Reading

References

Aug 1, 1992·The Journal of Clinical Investigation·A OgawaR H Unger
Jul 3, 2002·The Journal of Experimental Medicine·Hong JiChristophe Benoist
Dec 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Robert HannonRoderick J Flower
May 10, 2005·Immunology Letters·Subba Rao ChintalacharuvuChandrasekar Venkataraman
Sep 19, 2006·Best Practice & Research. Clinical Rheumatology·Danielle BurgerCem Gabay
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heather M SeitzGlenn K Matsushima
Apr 21, 2007·The Journal of Clinical Investigation·Jan P TuckermannGünther Schütz
Jul 17, 2007·Molecular and Cellular Endocrinology·Heike SchäckeKhusru Asadullah
Mar 1, 1945·Annals of the Rheumatic Diseases·A J Mester
Mar 3, 2010·Immunological Reviews·Beatrix Bartok, Gary S Firestein
Nov 2, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anna KleimanJan P Tuckermann
Nov 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ulrike BaschantJan P Tuckermann
Dec 14, 2011·The New England Journal of Medicine·Iain B McInnes, Georg Schett
May 16, 2012·The Journal of Clinical Investigation·Sofie VandevyverClaude Libert
Nov 14, 2012·Nature Reviews. Rheumatology·Nunzio Bottini, Gary S Firestein
Feb 1, 2013·Arthritis Research & Therapy·Rowan S HardyHong Zhou
Feb 12, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·A S VanniasingheV Bender
Jul 25, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura T DonlinLionel B Ivashkiv
Aug 3, 2014·Genome Biology·Benjamin J SchillerKeith R Yamamoto
Oct 9, 2014·Journal of Immunology Research·Seung Min JungJi Hyeon Ju
Nov 7, 2014·Cell Reports·Alexander V MisharinHarris Perlman
Dec 19, 2014·EMBO Molecular Medicine·Karmveer SinghKarin Scharffetter-Kochanek
Jul 18, 2015·Nature Communications·Sabine VettorazziJan P Tuckermann
Feb 5, 2016·Physiological Reviews·Kerstin HartmannJan P Tuckermann

❮ Previous
Next ❯

Citations

Jan 29, 2020·The Journal of Biological Chemistry·David Diaz-JimenezJohn A Cidlowski
Feb 12, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christina GlantschnigMarcel Scheideler
Aug 26, 2020·International Journal of Immunopathology and Pharmacology·Young Sun ChungKwang Won Jeong
Sep 6, 2018·Nature Reviews. Rheumatology·Rowan Hardy, Mark S Cooper
Feb 9, 2020·Nature Reviews. Rheumatology·Rowan S HardyMark S Cooper
Nov 21, 2019·International Journal of Molecular Sciences·Justine M WebsterRowan S Hardy
Aug 24, 2019·Frontiers in Immunology·Laura Escoter-TorresSabine Vettorazzi
Nov 5, 2019·Frontiers in Immunology·Mubashir AhmadJan Tuckermann
Jul 30, 2019·Frontiers in Immunology·Thibaut DesgeorgesBénédicte Chazaud
Oct 30, 2020·Drug Design, Development and Therapy·Qi-Shan WangTing-Yu Wang
Jan 22, 2021·Autoimmunity Reviews·Marie-Astrid BoutetFrédéric Blanchard
Dec 5, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mei YangWei Wei
Mar 13, 2021·Expert Review of Clinical Immunology·Maurizio CutoloEmanuele Gotelli
Sep 24, 2020·Bone Research·Eugenie MacfarlaneHong Zhou
Sep 5, 2021·Nature Reviews. Rheumatology·Jan Tuckermann, Ralf H Adams

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
RNASeq

Software Mentioned

RNASeq

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here