Lupus does not occur at birth, implicating that the clinical manifestations observed in lupus are due to the accumulation of pathological autoimmune events, decreases in regulatory mechanisms, or a combination of these processes. Notably, defects in two well established tolerance mechanisms, regulatory T cells (Tregs) and Suppressor of cytokine signaling-I (SOCSI)  have recently been implicated in lupus progression. Significantly, we have shown that SOCSI is critically involved in the stability of peripheral T regs. We also showed that a peptide which mimics SOCSI function could enhance Tregs numbers and prolong the survival of mice with lethal auto-inflammatory disease. Using a variety of lupus models we would like to establish whether SOCSI expression defects in Tregs or conventional T cells is correlated with lupus progression. Moreover, we propose to show that a peptide that mimics SOCSI function can inhibit lupus onset. Knowledge gained by this research could promote the development of additional lupus treatment strategies which target enhancement of SOCSI function. Additionally, the proposed studies can possibly provide mechanistic insight into preventing the development of a pro-lupus T cell repertoire, and thus lupus onset.