Exposure to inflammatory cytokines selectively limits GM-CSF production by induced T regulatory cells.
Bottom Line: Understanding processes that can limit this potentially deleterious effect of Treg cells in a therapeutic setting is therefore important.We show that iTreg cells can produce significant amounts of three proinflammatory cytokines (IFN-γ, GM-CSF and TNF-α) upon secondary TCR stimulation.Furthermore, we show that IL-6 and IL-27 individually, or IL-2 and TGF-β in combination, can mediate the selective loss of GM-CSF production by iTreg cells.
Affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.Show MeSH
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Mentions: Cytokine production by iTreg cells was investigated further during the initial Foxp3-induction culture. Of note, Foxp3-gfp expression consistently increased to over 90% within 72 h (Fig. 2A). At that time, cytokine production was low or undetectable, but rose markedly in cultures sampled at days 4 and 5 (Fig. 2B–D). This argues against the possibility that the sole source of IFN-γ, GM-CSF, and TNF-α was cells that had not gained Foxp3 expression. This was further shown by clear populations of cytokine+ Foxp3+ cells at the end of the 5-day culture (Fig. 2E–F). This was particularly the case for TNF-α (Fig. 2F).
Affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.