The Role of the Adrb3/IL6 Axis in the Impact of Psychosocial Stress on Lupus Pathogenesis

PROJECT SUMMARY Psychosocial stress has been well-documented to correlate with systemic lupus erythematosus (SLE) flares and poor SLE outcomes. How this occurs has not been well studied. We recently identified that psychosocial stress induces circulating IL6 produced by Adrb3-expressing brown adipocytes. Brown adipocyte-derived IL6 mediates immunometabolic reprogramming through hepatic IL6 signaling to support “fight or flight” responses to acute stress. We have generated preliminary data that chronic psychosocial stress may enhance mortality in murine models of SLE through this novel Adrb3/IL6 pathway. Here, we propose to dissect the role of the Adrb3/IL6 pathway in the impact of psychosocial stress on SLE pathogenesis in murine models. In addition to gaining biological insight into how psychosocial stress leads to increased immune activation in lupus, our studies would provide compelling pre-clinical data for potential human translation.