Role of Innate Lymphoid Cells in Rheumatoid Arthritis
Concept
Rheumatoid Arthritis (RA) severely impacts the life of affected individuals and current treatments are not effective in all patients. Fibroblast-like synoviocytes (FLS) are joint stromal cells which serve a key role in joint destruction during RA. Therefore, inflammatory mediators promoting FLS-driven joint destruction are considered important drug targets in RA. The group has evidence supporting a previously unrecognized mechanism of FLS activation by group 2 innate lymphoid cells (ILC2s), which challenges the current dogma regarding the role of ILC2 in RA. Thus, the objective is to determine if joint-localized ILC2 play a pathogenic, rather than protective, role in RA by promoting FLS-driven joint damage.
Facts and Figures
M Svensson
University of Gothenburg (UGOT)
mattias.svensson@rheuma.gu.se
Meet the Team
Objectives
- Aim 1. To establish the role of AREG-producing ILC2 in arthritis.
- Aim 2. To establish the presence of AREG-producing ILC2 in human RA.
- Aim 3. To demonstrate that ILC2-derived AREG promotes FLS aggressiveness.
Goals/Milestones
- Month 12: Established the pathogenic role of AREG-producing ILC2 in experimental arthritis (aim 1.1). Obtained initial evidence for an enrichment of AREG-producing ILC2 within the synovium of RA patients (aim 2.1 and 2.2).
- Month 24: Established that AREG-producing ILC2 activates a joint destructive behaviour in FLS in vivo (aim 1.2) and in vitro (aim 3.1).
- Month 30: Completed the analysis of AREG-producing ILC2 in human synovium (aim 2) and established that AREG-producing ILC2 promote cartilage degradation by RA FLS (aim 3.2).
- Month 36: Finalisation and publication of obtained results.
Patient Voice
Results from this project will establish a novel mechanism of disease in RA and thereby lead to the identification of new therapeutic targets, which can be exploited for the generation of new and effective therapies for RA and improve the lives of individuals affected by this disease.