RAC2 orchestrates immune cell actin remodeling and migration.

In this review, we comprehensively summarize how RAC2+ innate immune cells contribute to a spectrum of immune dysregulation and disease states across multiple organ systems in humans. Our lab has recently identified RAC2's critical role in immune cell biology in the context of human and murine wound healing and fibrosis, induced by aberrant mechanical signaling. Thus, we sought to investigate the role of RAC2 in human immune cells. Here, we summarize the effects of gain-of-function (GOF), loss-of-function (LOF), and null RAC2 mutations on neutrophil phenotypes. As such, we propose a novel mechanism for RAC2-dependent biphasic neutrophil migration, critical for these cells in migrating to sites of injury across many disease states, including wound healing and fibrosis. Innate immune cells circulate and home to injury sites during the initial healing phases in all organs, therefore, understanding RAC2 regulation of neutrophil functions may reveal new avenues for systemic immunomodulatory therapies to treat immune dysregulation, and to better characterize mechanisms of wound healing and fibrosis.