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.
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.
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.