Role of group 2 Innate Lymphoid Cells in the pathogenesis of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common autoimmune disease associated with chronic pain, functional disability, an overall reduced quality of life and increased need for medical care for affected individuals.

Immune cell-mediated activation of joint-lining fibroblast-like synoviocytes (FLS) is considered to play a key role in joint inflammation and destruction in RA.

I present preliminary evidence supporting a novel mechanism of FLS activation by the ILC2 subset of innate lymphoid cells (ILCs).

Thus, the objective of this proposal is to determine if ILC2 play an unrecognized pathogenic role in RA by promoting FLS-driven joint damage.

I will use a combination of mechanistic studies in mouse models of arthritis, studies on unique material from RA patients and functional studies in cell-based assays in order to; 1) demonstrate that ILC2 enhance development of arthritis in mice through the production of the fibroblast-activating growth factor amphiregulin (AREG), 2) provide evidence whether AREG-producing ILC2 are enriched within the synovium of RA patients and 3) establish a causative connection between AREG-producing ILC2 and joint-destructive behavior of FLS.

I’m confident that my expertise within RA immunopathology and the unique focus of this application will help accelerate the identification of novel disease mechanisms in RA, which is of critical importance for the development of new and more efficacious therapies.