Expression of PI3K signaling associated with T cells in psoriasis is inhibited by seletalisib, a PI3Kδ inhibitor, and is required for functional activity

Abstract

The phosphoinositide 3-kinase (PI3K) pathway plays a key role in many cellular processes, including cell proliferation, survival, and protein synthesis, with the PI3K isoform, PI3Kδ, involved in normal T-cell development and function (Jarmin et al., 2008, Lucas et al., 2016, Vanhaesebroeck et al., 2012). Evidence to suggest that PI3K signaling might play a role in psoriasis comes from reports of increased expression of phosphorylated protein kinase B, mammalian target of rapamycin, and ribosomal protein S6 (pS6), which are downstream in the PI3K signaling pathway, in lesional psoriatic skin compared with nonlesional skin and healthy controls (Buerger et al., 2013, Madonna et al., 2012, Rosenberger et al., 2007). In addition, PI3Kδ knock-in mice, expressing a catalytically inactive form of PI3Kδ (p110δD910A/D910A), and PI3Kγ knockout mice are greatly protected from imiquimod-induced psoriasis-like skin inflammation compared with wild-type mice (Roller et al., 2012).

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