SHIP1 and its role for innate immune regulation - novel targets for immunotherapy.

Phosphoinositide-3-kinase/AKT (PI3K/AKT) signaling plays key roles for the regulation of cellular activity in both health and disease. In immune cells, this PI3K/AKT pathway is critically regulated by the phosphoinositide phosphatase SHIP1, which has been reported to modulate the function of most immune subsets. In this review, we summarize our current knowledge of SHIP1 with a focus on innate immune cells, where we reflect on the most pertinent aspects described in the current literature. We also present the several small molecule agonists and antagonists of SHIP1 developed the last two decades, which have led to improved outcomes in several pre-clinical models of disease. We outline these promising findings and put them in relation with human diseases with unmet medical needs, where we discuss the most attractive targets for immune therapies based on SHIP1 modulation. This article is protected by copyright. All rights reserved.