The role of PI3Kγ in the immune system: new insights and translational implications.

The role of PI3Kγ in the immune system: new insights and translational implications.
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DOI:
10.1038/s41577-022-00701-8
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发表时间:
2022-11
期刊:
Nature reviews. Immunology
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其他
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在过去的二十年中,新的见解已经将磷酸肌苷3-激酶γ (PI3Kγ)定位为免疫和炎症的环境依赖性调节剂。x射线结构测定和药物开发的最新进展使得高度特异性PI3Kγ抑制剂的开发成为可能,目前第一批用于几种肿瘤适应症的临床试验。最近,在人类中发现了由PI3Kγ缺乏引起的单基因免疫疾病,并在小鼠中建立了模型。人类“失活PI3Kγ综合征”(IPGS)证实了PI3Kγ的免疫调节作用,并加强了该分子在调节巨噬细胞炎症细胞因子释放中的新定义作用。在这里,我们回顾了PI3Kγ在免疫系统中的功能,并讨论了我们对其作为治疗靶点的潜力的理解是如何演变的。
Over the past two decades, new insights have positioned phosphoinositide 3-kinase γ (PI3Kγ) as a context-dependent modulator of immunity and inflammation. Recent advances in X-ray structure determination and drug development have allowed for the development of highly specific PI3Kγ inhibitors, with the first now in clinical trials for several oncology indications. Recently, a monogenic immune disorder caused by PI3Kγ deficiency was discovered in humans and modeled in mice. Human ‘Inactivated PI3Kγ Syndrome’ (IPGS) confirms the immunomodulatory roles of PI3Kγ and strengthens newly defined roles of this molecule in modulating inflammatory cytokine release in macrophages. Here, we review the functions of PI3Kγ in the immune system and discuss how our understanding of its potential as a therapeutic target has evolved.
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期刊: Science (New York, N.Y.)
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