Selective targeting of PI3K δ suppresses human IL-17-producing T cells and innate-like lymphocytes and may be therapeutic for IL-17-mediated diseases.

Selective targeting of PI3Kδ suppresses human IL-17-producing T cells and innate-like lymphocytes and may be therapeutic for IL-17-mediated diseases. J Autoimmun. 2020 Apr 28;:102435 Authors: Chen S, Paveley R, Kraal L, Sritharan L, Stevens E, Dedi N, Shock A, Shaw S, Juarez M, Yeremenko N, Baeten D, Payne A Abstract The delta isoform of phosphoinositide 3-kinase (PI3Kδ) regulates various lymphocyte functions. Considering the key pro-inflammatory role of IL-17A and IL-17F cytokines in psoriasis and spondyloarthritis (SpA), we investigated the potential of PI3Kδ blockade to suppress IL-17A, IL-17F and associated pro-inflammatory cytokines that could synergize with IL-17A and IL-17F. Using in vitro studies with primary human cells and ex vivo studies with inflamed target tissues, we assessed if seletalisib, a selective PI3Kδ inhibitor, suppresses cytokine production by T cells and innate-like lymphocytes, and if seletalisib modulates the inflammatory responses in stromal cell populations in psoriasis (human dermal fibroblasts (HDF)) and SpA (fibroblast-like synoviocytes (FLS)). In vitro, seletalisib inhibited the production of pro-inflammatory cytokines, including IL-17A and IL-17F, from peripheral blood mononuclear cells (PBMCs), T helper 17 (Th17) cells as well as γδ-T cells and mucosal-associated invariant T cells. This inhibition resulted in decreased inflammatory activation of HDF in co-culture systems. Seletalisib was also ...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research