首页 | 本学科首页   官方微博 | 高级检索  
     


Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis
Authors:Theo S Plantinga  Jaap Fransen  Nozomi Takahashi  Rinke Stienstra  Piet L van Riel  Wim B van den Berg  Mihai G Netea  Leo AB Joosten
Affiliation:1. Departments of Surgery, Pathology, Microbiology and Immunology, University of Western Ontario, 1393 Western Road, N6G 1G9, London, Ontario, Canada
3. Medistem Inc, 9255 Towne Centre Drive, 92121-3038, San Diego, CA, USA
2. Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University Health Network, 1E423 - 399 Bathurst Street, M5T 2S8, Toronto, Ontario, Canada
4. Multi-Organ Transplant Program, London Health Sciences Centre, 339 Windermere Road, N6A 5A5, London, Ontario, Canada
5. Transplantation and Regenerative Medicine, Lawson Health Research Institute, 339 Windermere Road, N6A 5A5, London, Ontario, Canada
Abstract:

Introduction

We have previously demonstrated that ex vivo inhibition of costimulatory molecules on antigen-pulsed dendritic cells (DCs) can be useful for induction of antigen-specific immune deviation and suppression of autoimmune arthritis in the collagen induced arthritis (CIA) model. The current study evaluated a practical method of immune modulation through temporary systemic inhibition of the costimulatory molecule CD40.

Methods

Mice with collagen II (CII)-induced arthritis (CIA) were administered siRNA targeting the CD40 molecule. Therapeutic effects were evaluated by clinical symptoms, histopathology, Ag-specific T cell and B cell immune responses.

Results

Systemic administration of CD40-targeting siRNA can inhibit antigen-specific T cell response to collagen II, as well as prevent pathogenesis of disease in both a pre- and post-immunization manner in the CIA model. Disease amelioration was associated with suppression of Th1 cytokines, attenuation of antibody production, and upregulation of T regulatory cells.

Conclusions

These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity.
Keywords:
本文献已被 SpringerLink 等数据库收录！
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号