查看文章

Interleukin (IL)-9 producing CD4+ T cells are a novel subset of T helper (TH) cells that develops independently of the TH1, TH2, TH17 and regulatory T cell lineages. Similar to the murine model, TGF-β and IL-4 directed human naïve CD4+ T cells to produce IL-9. Whereas IL-4 suppressed TGF-β-induced Foxp3 expression, TGF-β failed to inhibit IL-4-mediated upregulation of the TH2 transcription factor GATA-3. Addition of IL-1β, IL-6, IL-10, IFN-α, IFN-β or IL-21 to TH 9 differentiation, while the TH 9 polarizing conditions augmented TH 1 associated cytokines IFN-γ and IL-27 partially suppressed IL-9 production. Given that T cells are a primary source of IL-21, IL-21 expression was analyzed under TH9 polarizing conditions in the context of inflammatory cytokines. Surprisingly, type I interferons induced elevated levels of IL-21, and blockade of IL-21 abrogated their ability to enhance TH9 differentiation. Taken together, these data indicate a complex cytokine network in the regulation of human IL-9-producing CD4+ T cells.