SHIP1 and its role for innate immune regulation-Novel targets for immunotherapy

Phosphoinositide-3-kinase/AKT (PI3K/AKT) signaling plays key roles in 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 several small-molecule agonists and antagonists of SHIP1 developed over the last two decades, which have led to improved outcomes in several preclinical models of disease. We outline these promising findings and put them in relation to human diseases with unmet medical needs, where we discuss the most attractive targets for immune therapies based on SHIP1 modulation. The inositol phosphatase SHIP1 pleiotropically regulates different immune cell types involved in several disorders. In this review, we integrate the current knowledge on SHIP1-mediated regulation of innate immunity and explore novel avenues for the therapeutic use of SHIP1 agonists or antagonists to ameliorate specific inflammatory diseases.#image

Automated summary

The review summarizes the current knowledge of the phosphoinositide phosphatase SHIP1 and its role in regulating innate immune cells. It also discusses the development of small-molecule agonists and antagonists targeting SHIP1, and explores the potential use of SHIP1 modulation in immune therapies for human diseases with unmet medical needs.