2013 New Treatments, T Cells
Regulation of SLE Through SOCS1 Mimetic Peptides
The Study and What It Means to Patients
"We are exploring a new approach to treating lupus by boosting the numbers of immune cells that specifically suppress unwanted immune responses."
While certain T cells of the immune system are guilty of launching attacks on the body, other T cells have precisely the opposite effect. These regulatory T cells police the immune system and suppress potentially dangerous self-directed immune responses. There is growing evidence that lupus patients are deficient in this type of cell, which may explain their susceptibility to autoimmunity. We are testing whether we can prevent lupus in mice by treating them with an immune cell protein (SOCS1) that we found boosts the number of regulatory T cells. If successful, this approach could lead to new therapeutic solutions to lupus.
Lupus does not occur at birth, indicating 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-1 (SOCS1), have recently been implicated in lupus progression. Significantly, we have shown that SOCS1 is critically involved in the stability of peripheral Tregs. We also showed that a peptide which mimics SOCS1 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 SOCS1 expression defects in Tregs or conventional T cells is correlated with lupus progression. Moreover, we propose to show that a peptide that mimics SOCS1 function can inhibit lupus onset. Knowledge gained by this research could promote the development of additional lupus treatment strategies which target enhancement of SOCS1 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.