Role of IL-24 in NK cell activation and its clinical implication in systemic lupus erythematosus

Abstract

Objectives: Interleukin (IL)-24 has been considered as an inflammatory cytokine in autoimmune diseases. However, conflicting data exist and its biological function remains controversial. Additionally, little is known about its functional impact on natural killer (NK) cells. The aim of this study was to investigate the role of IL-24 in NK cell activation and its clinical implication in systemic lupus erythematosus (SLE).

Methods: Serum cohort consisting of 299 SLE patients, 214 RA patients, and 159 healthy controls (HCs) and plasma cohort consisting of 70 SLE patients, 82 RA patients, and 123 HCs were included in evaluating IL-24 concentrations. Impact of IL-24 on NK cell activation was assessed in two NK cell subsets, i.e., CD56^dimCD16⁺ and CD56^brightCD16^- NK cells. Human NK-92 cell line was applied to evaluate functional potential of IL-24 on NK cell migration and invasion.

Results: Serum and plasma levels of IL-24 were comparable between patients with SLE or RA and HCs. While recombinant human (rh) IL-2 consistently induced an increased expression of CD69 on both CD56^dimCD16⁺ and CD56^brightCD16^- cells derived from both healthy subjects and patients with SLE, IL-24 alone was insufficient to activate the CD56^dim and CD56^bright NK cells. Similarly, while the migratory NK-92 cell numbers were significantly increased with rhIL-2 stimulation, IL-24 alone was unable to enhance NK-92 cell migratory and invasive capacity.

Conclusion: Our data indicate that there were no significant differences in serum and plasma concentrations of IL-24 between SLE patients and healthy controls. Recombinant IL-24 has no effect on NK cell activation and migration. Key points • This is the first study to investigate functional potential of IL-24 on NK cell activation. • Recombinant IL-24 lacks functional capacity on NK cell activation in either CD56^dimCD16⁺ or CD56^brightCD16^- NK cell subsets derived from both healthy subjects and patients with SLE. • No significant differences in serum and plasma levels of IL-24 between SLE patients and healthy controls.

Keywords: Cell activation; IL-24; NK cells subsets; Systemic lupus erythematosus.