Mechanisms underlying interferon-induced T peripheral helper cell differentiation

PROJECT SUMMARY Systemic lupus erythematosus (SLE) is a highly morbid autoimmune disease. Despite recent advances, there is a critical unmet need to discover novel therapies that precisely target the pathophysiological basis of this disease. Emerging data suggest the importance of a relatively recently discovered cell type, the T peripheral helper (Tph) cell. It is pathologically expanded in lupus patients, highly correlated with disease activity, and produces factors that support autoantibody production. Our preliminary data suggest that one of the reasons why these cells are expanded in these patients is the high levels of circulating type I interferon, a cytokine. In this proposal, we will apply cutting-edge biochemical, epigenetic, and genetic approaches to human T cells (both healthy controls and patient samples). We will utilize these high-dimensional datasets to elucidate the molecular mechanisms by which IFN supports the production and expansion of this cell type. These data will likely reveal novel therapeutic approaches that can be leveraged for future therapies.