ICMI 2015

T.53 Reduced in vitro Polarization of Salmonella-Specific IL-17 Secreting CD4+ T (Th17) cells by Salmonella-Infected Dendritic cells Derived from Crohn’s Disease Patients

Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Aito Ueno, PhD , University of Calgary, Calgary, AB, Canada
Humberto Jijon, MD PhD , University of Calgary, Calgary, AB, Canada
Subrata Ghosh, MD , University of Calgary, Calgary, AB, Canada
Introduction

Aberrant dendritic cell (DC) presentation of bacterial antigens may contribute to inflammatory bowel disease (IBD) pathogenesis. The balance between effector Th17 cells and FoxP3+ regulatory T cells (Treg) is required the gut homeostasis and depends on DC cues. We reported the increased prevalence of circulating Treg and Th17 in Crohn’s disease (CD) patients compared to healthy controls (HC), yet the role of DC-bacterial interactions are still unclear.  Our aim was to assess T cell profiles responding to in vitro DC infection with salmonella in CD patients.

Methods

Monocyte-derived dendritic cells (Mo-DC) were differentiated from peripheral blood of CD (n=13) and HC (n=16) using IL-4/GM-CSF and infected with salmonella Typhimuriumfor 24 hours. The infected Mo-DC were co-cultured with autologous naïve CD4+ T cells for an additional 7-days and T cell polarization  assessed using FACS.

Results and conclusions

Mo-DC from CD patients were impaired in their ability to polarize CD4+ T cells towards Th17 and Th1 following salmonella infection compared to that from HC. This suggests an impaired ability to generate robust antibacterial responses in CD patients.  Impaired generation of salmonella-specific Th17 by infected DC does not contribute to the increased circulating pan-Th17 in CD patients