Michael Rehli • Dept. Internal Medicine III • University Hospital • F.-J.-Strauss Allee 11 • 93053 Regensburg
Our work on gene regulation and epigenetics primarily focuses on two haematopoietic cell lineages: Mononuclear phagocytes & CD4+ T cells.
Our lab has a long-standing interest in the biology of mononuclear phagocytes. Though heterogeneous in morphology, biochemistry and function, most mononuclear phagocytes originate from blood monocytes. These cells migrate into almost all tissues and mature into the various types of tissue macrophages or two other specialized cell types: the antigen-presenting dendritic cells or the multinucleated bone-resorbing osteoclasts. Mononuclear phagocytes fulfill important roles in development, tissue homeostasis, inflammation and wound healing and are a major cell population in most of the tissues in the body.
Natural CD4+CD25+ regulatory T (Treg) cells play a fundamental role in maintaining immunological self tolerance and immune homeostasis. They develop in the thymus as an independent CD4+ T cell lineage and represent a prime example for epigenetic regulation. The functional program of Treg cells is at least partially controlled by miRNA pathways, and continuous expression of the lineage-directing transcription factor FOXP3 is dependent on its DNA methylation status at a methylation-sensitive, Treg cell-specific enhancer.
Our identification of differential DNA methylation in human conventional CD4+ T cells (Tconv) and CD4+CD25+ regulatory T cells (Treg) and its frequent correlation with methylation-sensitive enhancer activity suggests a general role for DNA methylation in controlling lineage-specific gene expression by restricting promoter-distal regulatory elements. Ongoing work (in collaboration with Petra Hoffmann & Matthias Edinger in our Department) aims at understanding how differential epigenetic patterns are established and maintained. Since the adoptive transfer of in vitro expanded regulatory T (Treg) cells is a promising treatment option for autoimmune as well as alloantigen-induced diseases, we’re also trying to understand why, when, and how in vitro expanded Treg cells convert into other T cell types.