Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
TGF-β–dependent suppressive function of Tregs requires wild-type levels of CD18 in a mouse model of psoriasis
Honglin Wang, … , Johannes M. Weiss, Karin Scharffetter-Kochanek
Honglin Wang, … , Johannes M. Weiss, Karin Scharffetter-Kochanek
Published June 2, 2008
Citation Information: J Clin Invest. 2008;118(7):2629-2639. https://doi.org/10.1172/JCI34916.
View: Text | PDF
Research Article Dermatology

TGF-β–dependent suppressive function of Tregs requires wild-type levels of CD18 in a mouse model of psoriasis

  • Text
  • PDF
Abstract

Dysfunctional Tregs have been identified in individuals with psoriasis. However, their role in the pathogenesis of the disease remains unclear. Here we explored the effect of diminished CD18 (β2 integrin) expression on the function of CD4+CD25+CD127– Tregs using the Cd18 hypomorphic (Cd18hypo) PL/J mouse model of psoriasis that closely resembles the human disease. We found that reduced CD18 expression impaired cell-cell contact between Tregs and DCs. This led to dysfunctional Tregs, which both failed to suppress the pathogenic T cells and promoted the onset and severity of the disease. This failure was TGF-β–dependent, as Tregs derived from Cd18hypo PL/J mice had diminished TGF-β1 expression. Adoptive transfer of Tregs expressing wild-type levels of CD18 into affected Cd18hypo PL/J mice resulted in a substantial improvement of the psoriasiform skin disease, which did not occur upon coinjection of the cells with TGF-β–specific neutralizing antibody. Our data indicate a primary dysfunction of Cd18hypo Tregs, allowing subsequent hyperproliferation of pathogenic T cells in the Cd18hypo PL/J mouse model of psoriasis. This study may provide a step forward in our understanding of the unique role of CD18 expression levels in avoiding autoimmunity.

Authors

Honglin Wang, Thorsten Peters, Anca Sindrilaru, Daniel Kess, Tsvetelina Oreshkova, Xue-Zhong Yu, Anne Maria Seier, Heike Schreiber, Meinhard Wlaschek, Robert Blakytny, Jan Röhrbein, Guido Schulz, Johannes M. Weiss, Karin Scharffetter-Kochanek

×

Figure 1

Adoptive transfer of Cd18wt CD4+CD25+CD127– Tregs into affected Cd18hypo mice resolves the psoriasiform skin disease.

Options: View larger image (or click on image) Download as PowerPoint
Adoptive transfer of Cd18wt CD4+CD25+CD127– Tregs into affected Cd18hypo...
(A) Representative clinical pictures of a Cd18hypo mouse with severe psoriasiform skin disease before (left panel) and almost complete resolution 42 days after the first adoptive transfer with Tregs from Cd18wt mice (right panel). An adapted PASI score was used to assess the severity of the psoriasiform phenotype before and after adoptive transfer with Cd18wt Tregs (B) or Cd18hypo Tregs (C). Data are representative of 3 independent experiments. (D) An improvement of the psoriasiform skin disease in affected Cd18hypo mice was observed after intradermal injection of Cd18wt Tregs once weekly for 3 weeks. (E and F) The adapted PASI score of affected Cd18hypo mice treated with Cd18wt Tregs is significantly reduced compared with that of mice treated with Cd18hypo Tregs. **P < 0.01, using Student’s t test. Original magnification, × 1 (A and D).
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts