AbstractsBiology & Animal Science

Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for patients with hematologic malignancies, aplastic anaemia, and congenital immunodeficiency disorders. One of the major serious morbidities associated with HCT is the development of acute or chronic graft-versus-host disease (GvHD). The pathophysiology of GvHD is complex and not fully understood. The role of Th17 cells during GvHD is discussed controversially and still remains unclear. In this study, the induction of Th17 cells by monocytes of patients with GvHD in vitro was analysed demonstrating that monocytes isolated from patients with acute skin and intestinal GvHD stage I-IV or chronic GvHD induce significantly increased levels of Th17 cells compared to patients without GvHD after HCT and healthy controls. Several studies suggest using the determined levels of regulatory (Treg) cells and the ratio of Th17 cells to Treg cells in the peripheral blood of patients as diagnostic markers for GvHD. However, the data of the present study have demonstrated that the determined percentages of Treg cells in peripheral blood mononuclear cells (PBMCs) isolated from patients with acute GvHD do not differ from the assessed percentages of Treg cells in PBMCs of healthy donors and patients without GvHD after HCT. By contrast, the percentages of Treg cells in PBMCs from patients with extensive chronic GvHD seem to be increased in comparison to the healthy controls and the non-GvHD group. The results of the present work further indicate that the calculated ratios of Th17 cells to Treg cells are not altered in patients with acute or chronic GvHD compared to patients without GvHD after HCT. Development and progression of GvHD is mediated by multiple cellular and inflammatory effectors. However, several of these molecules are still unknown. Previous studies have demonstrated that S100 proteins act as innate amplifier of inflammation and play an important role in many inflammatory diseases such as inflammatory bowel disease or rheumatoid arthritis. These proinflammatory S100 proteins belong to the group of Damage Associated Molecular Pattern (DAMP) molecules and are released by activated or damaged phagocytes under conditions of cell stress during infections and autoimmune diseases. Therefore, expression levels of S100 proteins in monocytes and the presence of S100 proteins in the stool, serum and bowel tissue were investigated in patients with acute or chronic GvHD and compared to healthy controls and patients without GvHD after HCT. Additionally, the influence of S100 proteins on monocyte-mediated induction of Th17 cells was analysed. The data of this study demonstrate that the expression of S100 proteins is increased in monocytes from patients with GvHD compared to the controls. Overall, elevated levels of S100 proteins can be detected in the serum, stool and bowel tissue of patients with GvHD demonstrating the release of these phagocyte-specific proteins during GvHD. Furthermore, S100 proteins were found to bind to toll-like receptor 4 (TLR4) on…