Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

2017

The nuclear receptor PPARγ selectively inhibits Th17 differentiation in a T cell–intrinsic fashion and suppresses CNS autoimmunity

2009

T helper cells secreting interleukin (IL)-17 (Th17 cells) play a crucial role in autoimmune diseases like multiple sclerosis (MS). Th17 differentiation, which is induced by a combination of transforming growth factor (TGF)-beta/IL-6 or IL-21, requires expression of the transcription factor retinoic acid receptor-related orphan receptor gamma t (ROR gamma t). We identify the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) as a key negative regulator of human and mouse Th17 differentiation. PPAR gamma activation in CD4(+) T cells selectively suppressed Th17 differentiation, but not differentiation into Th1, Th2, or regulatory T cells. Control of Th17 differentia…

Virally Infected Mouse Liver Endothelial Cells Trigger CD8+ T-Cell Immunity

2009

Background & Aims Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8 + T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8 + T-cell activation upon such stimulation. Methods Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo…

Liver-primed memory T cells generated under noninflammatory conditions provide anti-infectious immunity.

2013

SummaryDevelopment of CD8+ T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling thro…