PhD defence T.C.E. (Timo) Zondag

Below is a brief summary of the dissertation:

Histiocytes are a group of hematopoietic cells consisting of dendritic cells, Langerhans cells (LCs), and macrophages. When (a subset of) these cells acquire pathogenic features, the subsequent disease is classified as a histiocytic disorder. This thesis has a main focus on two of the most prevalent histiocytic disorders, HLH and LCH. HLH is characterized by a pathological, hyperinflammatory state with high mortality rates. Genetic predisposition and environmental triggers such as viruses and malignancies collectively add to reach a certain threshold. Above this threshold the immune response spins out of control, leading to a severe clinical state called HLH. LCH on the other hand, is a neoplastic disease where lesions are formed consisting of pathognomonic LCH-cells in a background of immune cells and sometimes fibrosis. The pathophysiology is largely driven by functionally aberrant histiocytes expressing somatic, activating MAPK-pathway mutations.