Projects per year
Abstract / Description of output
Interest in manipulating the immunosuppressive powers of Foxp3-expressing T regulatory (Treg) cells as an immunotherapy has been tempered by their reported ability to produce pro-inflammatory cytokines when manipulated in vitro, or in vivo. Understanding processes that can limit this potentially deleterious effect of Treg cells in a therapeutic setting is therefore important. Here we have studied this using induced (i)Treg cells in which de novo Foxp3 expression is driven by T-cell receptor (TCR)-stimulation in vitro in the presence of TGF-β. We show that iTreg cells can produce significant amounts of three pro-inflammatory cytokines (IFN-γ GM-CSF and TNF-α) upon secondary TCR stimulation. GM-CSF is a critical T-cell-derived cytokine for the induction of experimental autoimmune encephalomyelitis (EAE) in mice. Despite their apparent capacity to produce GM-CSF, myelin autoantigen-responsive iTreg cells were unable to provoke EAE. Instead, they maintained strong suppressive function in vivo, preventing EAE induction by their CD4+Foxp3− counterparts. We identified that although iTreg cells maintained the ability to produce IFN-γ and TNF-α in vivo, their ability to produce GM-CSF was selectively degraded upon antigen stimulation under inflammatory conditions. 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.
Original language | English |
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Pages (from-to) | 3342–3352 |
Journal | European Journal of Immunology |
Volume | 44 |
Issue number | 11 |
Early online date | 1 Oct 2014 |
DOIs | |
Publication status | Published - 14 Nov 2014 |
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Dive into the research topics of 'Exposure to inflammatory cytokines selectively limits GM-CSF production by induced T regulatory cells'. Together they form a unique fingerprint.Projects
- 2 Finished
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The role of T-bet in Foxp3+ regulatory cell-mediated protection from autoimmune inflammation
Anderton, S. & O'Connor, R.
1/04/12 → 31/03/15
Project: Research
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Immune cell interactions in the inflammed CNS
Anderton, S. & O'Connor, R.
1/04/09 → 30/09/14
Project: Research