Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides

TLDR

Th17 cells are a distinct lineage of effector CD4⁺ T cells that produce interleukin‑17. The study examined how combinations of IL‑22, IL‑17A, and IL‑17F affect antimicrobial peptide expression in primary keratinocytes. IL‑22 expression is triggered by TGF‑β signaling in the presence of IL‑6 and other cytokines, and the authors stimulated primary keratinocytes with IL‑22, IL‑17A, and IL‑17F to evaluate antimicrobial peptide induction. Th17 cells produce IL‑22 at higher levels than Th1/Th2 cells, its expansion depends on IL‑23, and IL‑22 is coexpressed with IL‑17A/F; together they synergistically induce antimicrobial peptides such as beta‑defensin 2, S100A9, S100A7, and S100A8, underscoring IL‑22’s role in skin innate immunity.

Abstract

Th17 cells are a distinct lineage of effector CD4(+) T cells characterized by their production of interleukin (IL)-17. We demonstrate that Th17 cells also expressed IL-22, an IL-10 family member, at substantially higher amounts than T helper (Th)1 or Th2 cells. Similar to IL-17A, IL-22 expression was initiated by transforming growth factor beta signaling in the context of IL-6 and other proinflammatory cytokines. The subsequent expansion of IL-22-producing cells was dependent on IL-23. We further demonstrate that IL-22 was coexpressed in vitro and in vivo with both IL-17A and IL-17F. To study a functional relationship among these cytokines, we examined the expression of antimicrobial peptides by primary keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F. IL-22 in conjunction with IL-17A or IL-17F synergistically induced the expression of beta-defensin 2 and S100A9 and additively enhanced the expression of S100A7 and S100A8. Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity.