In Situ Contribution of Plasmacytoid Dendritic Cells in Gut Acute Graft Versus Host Disease: Relation with the Th17 Immune Response
Celine Bossard, Florent Malard, Jessy Arbez, Patrice Chevalier, Thierry Guillaume, Jacques Delaunay, Jean-Francois Mosnier, Philippe Saas, Mohamad Mohty, Beatrice Gaugler. EA 4273 Biometadys, Université de Nantes, Faculté de Médecine, Nantes, France; INSERM UMR892, Nantes, France; INSERM UMR 645, Besançon, France; Service d'Hématologie Clinique, CHU Hotel Dieu, Nantes, France
Background: Acute GVHD (aGVHD) after allogeneic stem cell transplantation (allo-SCT) is an exaggerated immune response against alloantigens involving dysregulation of inflammatory cytokine cascades. The role of Th17 cells in human aGVHD as well as the role of Plasmacytoid Dendritic Cells (PDC), which play an important role in triggering Th17-related cytokines and autoimmune diseases, is not yet established in the aGVHD setting. This prompted us to analyze Th17 cells and PDC in gastrointestinal biopsies taken from patients with aGVHD.
Design: Gastrointestinal biopsies of 23 patients who underwent allo-SCT for different hematological diseases were analyzed for the density of PDC and Th17 cells by immunohistochemistry. To identify the Th17 cells and PDC, biopsies were tested for the expression of CD161, CCR6, RORγ, and CD123 respectively. A quantitative evaluation of antigens expression was performed by counting the number of positive cells/field at 200 magnifications for each sample. The density of PDC and Th17 cells was correlated to the morphological grade of aGVHD.
Results: Eighteen patients had a histologically proven gastrointestinal aGVHD. The remaining 5 patients did not have clinical and histological signs of aGVHD, and thus were used as controls. Higher number of RORγ+ (p=0.02) and CD161+ (p=0.009) cells were counted in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD. In parallel, we found a significant increase of CD123+ PDCs in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD (p=0.012), this increased number of PDC paralleled the morphological grade of aGVHD.
Conclusions: The current study shed some light on the role of Th17 cells in the context of gastrointestinal aGVHD. We showed that Th17 cells infiltrate intestinal mucosa from patients with aGVHD and was associated with an increased number of PDCs, suggesting a potential new pathophysiological link between PDCs and Th17 immune response in the context of gastrointestinal aGVHD. This is consistent with studies showing that PDCs can drive the differentiation of Th17 cells. These data raise the prospect of future innovative approaches to optimize immunosuppression regimens for the treatment or prophylaxis of aGVHD by targeting PDCs and the Th17 immune response.
Monday, March 19, 2012 1:00 PM
Poster Session II # 106, Monday Afternoon