IL-12 inhibits the TGF-beta-dependent T cell developmental programs and skews the TGF-beta-induced differentiation into a Th1-like direction
Abstrakt
Development and differentiation of Th cells is highly plastic and strictly regulated by cytokines. We show negative regulation of TGF-beta-dependent differentiation programs by IL-12.
Development of TGF-b-induced regulatory T cells (iTregs) or TGF-b/IL-6-activated Th17 cells from purified mouse CD4+CD25- T cells stimulated with anti-CD3 was abrogated by IL-12, establishing different developmental program. IL-12 inhibited expression of lineage-specific transcription factors Foxp3 and RORgt in developing Tregs and Th17 cells.
IL-12 altered development of iTregs and Th17 cells even added after 48 h. Cells activated by TGF-b and IL-12 had increased expression of T-bet, produced Th1 cytokines IFN-g and IL-2 and expressed IL-18 receptor and C-C chemokine receptor type 5.
Cells activated by both TGF-b and IL-12 stimulated macrophages to produce nitric oxide. IL-12 is shown as superior cytokine able to skew ongoing TGF-b-dependent iTreg or Th17 developmental program to Th1-like direction.