Towards new treatments for rheumatoid arthritis in postmenopausal women – targeting a key role for interleukin-17

The peak incidence of rheumatoid arthritis (RA) in women coincides with the time of menopause and treatment with estrogen is beneficial by reducing both joint inflammation and osteoporosis. Unfortunately, estrogen therapy is strongly discouraged due to severe side-effects.

The goal of this project is to uncover the immunological mechanisms underlying the beneficial effects of estrogen on inflammation and bone loss in RA in order to provide opportunities to develop new therapies.IL-17 producing T cells (Th17 cells) are involved in the pathogenesis of both arthritis and osteoporosis.

However, the effects of estrogen on Th17 cells are largely unknown.

Studies in my laboratory strongly implicate Th17 cells in the RA-reducing effects of estrogen, as estrogen-mediated inhibition of experimental arthritis is associated with reduced numbers of Th17 cells exiting the lymph nodes.

We will define the specific mechanisms involved in this phenomenon and determine whether circulating pre-osteoclasts and Th17 cells can be used as markers to predict development of osteoporosis in RA patients.New treatment strategies that target both inflammation and osteoporosis in RA are needed.

In this project, we will pave the way for such therapies by determining whether inhibition of Th17 cells is associated with the protective effects of estrogen in RA.

The project is novel and innovative and will have significant implications for a variety of inflammatory conditions and associated osteoporosis.