Th22 Cells Promote in vitro Proliferation and Cytokine Secretion in HaCaT and HRMC cells via Production of IL-22 and Stimulation of PI3K/AKT Signaling

Background: T helper (Th) 22 cells function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact role remains unclear. We examined in vitro interactions of Th22 cells with different target cells. Methods: Flow cytometry was used to isolate Th22 cells from the peripheral blood mononuclear cells (PBMCs) of 5 healthy subjects. The optimal co-culture ratio of effector:target (E:T) cells and the optimal co-culture concentration of recombinant interleukin (rIL) -22 were determined. The levels of IL-22, proliferation of target cells, and the levels proinflammatory cytokines in different culture systems with human keratinocyte cells (HaCaT) and human renal mesangial cells (HRMC) were determined. Western blotting was used to assess changes in the levels of proteins in the PI3K/AKT pathway. Results: The levels of IL-22 were greater when HaCaT and HRMC cells were co-cultured with Th22 cells or rIL-22, and co-culturing with contact had a greater effect than co-culturing without contact. The levels of cytokines were also significantly greater when target cells were co-cultured with Th22 cells. IL-22mAb reversed the effect of IL-22. Th22 cells significantly activated PI3K/AKT signaling in HaCaT and HRMC cells; LY294002 (an inhibitor of this pathway) reversed this effect and also downregulated the levels of proinflammatory cytokines; IL-22mAb had a similar but weaker effect. Conclusions: Our results suggest that Th22 cells promote cell proliferation and secretion of pro-inflammatory cytokines of their target cells via IL-22-mediated stimulation of PI3K/AKT signaling.