Selective ERK activation suppresses inflammatory arthritis via tolerogenic dendritic cells and antigen-specific regulatory T cells

F. Arce, Karine Breckpot, H. Stephenson, K. Karwacz, M. Collins, D. Escors

Research output: Chapter in Book/Report/Conference proceedingConference paper

Abstract

OBJECTIVE: Most therapeutic treatments for autoimmune arthritis rely on immunosuppressive drugs which have side effects. Although a previous study by our group showed that specific ERK activation suppressed immune responses, its application in a therapeutic setting has never been tested. The aim of the present study was to define the ERK-dependent immunosuppressive mechanisms and apply selective ERK activation for the treatment of experimental inflammatory arthritis

METHODS: A constitutively active ERK activator was co-expressed with a model antigen using lentivectors. Immunosuppressive mechanisms were characterized at the level of dendritic cell function, differentiation of antigen-specific Tregs and inhibition of inflammatory T cells. Administration of the ERK activator with antigen to suppress experimental inflammatory arthritis was tested in a mouse model

RESULTS: Selective ERK activation induced mouse and human DCs to secrete bioactive TGF-B, required to suppress T cell responses and differentiate antigen-specific Tregs. Tregs strongly proliferated after antigen re-encounter in inflammatory conditions and exhibited antigen-dependent suppressive activities. Inflammatory arthritis was effectively inhibited through antigen-specific mechanisms. Finally, we showed that our strategy did not rely on identifying the initiating arthritogenic antigen. Equivalent mechanisms in human DCs were demonstrated, setting the scene for rapid translation to patients with rheumatoid arthritis.

CONCLUSION: This strategy resulted in an effective therapeutic protocol with substantial advantages over DC or T cell vaccination.
Original languageEnglish
Title of host publicationESGCT 2010
Pages273-273
Number of pages1
Publication statusPublished - 25 Oct 2010
EventFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden
Duration: 21 Sep 200925 Sep 2009

Conference

ConferenceFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet
CountrySweden
CityStockholm
Period21/09/0925/09/09

Keywords

  • ERK
  • arthritis
  • dendritic cells
  • T-cells

Fingerprint

Dive into the research topics of 'Selective ERK activation suppresses inflammatory arthritis via tolerogenic dendritic cells and antigen-specific regulatory T cells'. Together they form a unique fingerprint.

Cite this