The development and differentiation of T helper (Th) cell subsets is a highly plastic process which is strictly regulated by cytokines. Here we show that the transforming growth factor β (TGF-β)-dependent differentiation programs are negatively regulated by interleukin-12 (IL-12). The development of TGF-β-induced regulatory T cells (iTregs) or TGF-β/IL-6 activated Th17 cells from purified mouse CD4(+)CD25(-) T cells, stimulated with monoclonal antibody anti-CD3, was abrogated in the presence of IL-12 and a different developmental program was established. On the molecular level, IL-12 inhibited the expression of the lineage specific transcription factors Foxp3 and RORγt in developing Tregs and Th17 cells, respectively. Moreover, IL-12 was able to alter the development of iTregs and Th17 cells even when added to the differentiating cells after 48h of the culture. The cells activated in the presence of TGF-β and IL-12 had an increased expression of the Th1 transcription factor T-bet, produced Th1 cytokines interferon γ and IL-2 and expressed IL-18 receptor and C-C chemokine receptor type 5 which are the phenotypic markers characteristic for Th1 cells. Furthermore, the cells activated in the presence of both TGF-β and IL-12, and not of TGF-β only, stimulated macrophages to produce nitric oxide. Altogether, these results indicate that IL-12 is a superior cytokine that has the ability to skew the already ongoing TGF-β-dependent iTreg or Th17 developmental program into Th1-like direction.
- MeSH
- buněčná diferenciace účinky léků imunologie MeSH
- buňky Th17 cytologie účinky léků imunologie metabolismus MeSH
- exprese genu účinky léků imunologie MeSH
- forkhead transkripční faktory genetika imunologie metabolismus MeSH
- interferon gama genetika imunologie metabolismus MeSH
- interleukin-12 imunologie farmakologie MeSH
- interleukin-2 genetika imunologie metabolismus MeSH
- interleukin-6 genetika imunologie metabolismus MeSH
- jaderné receptory - podrodina 1, skupina F, člen 3 genetika imunologie metabolismus MeSH
- makrofágy cytologie účinky léků imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- oxid dusnatý biosyntéza MeSH
- receptory CCR5 genetika imunologie metabolismus MeSH
- receptory interleukinu-18 genetika imunologie metabolismus MeSH
- regulační T-lymfocyty cytologie účinky léků imunologie metabolismus MeSH
- signální transdukce účinky léků imunologie MeSH
- Th1 buňky cytologie účinky léků imunologie metabolismus MeSH
- transformující růstový faktor beta imunologie farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- forkhead transkripční faktory MeSH
- Foxp3 protein, mouse MeSH Prohlížeč
- interferon gama MeSH
- interleukin-12 MeSH
- interleukin-2 MeSH
- interleukin-6 MeSH
- jaderné receptory - podrodina 1, skupina F, člen 3 MeSH
- oxid dusnatý MeSH
- receptory CCR5 MeSH
- receptory interleukinu-18 MeSH
- transformující růstový faktor beta MeSH
