Investigating the role of the transcription factor Rorα in macrophages in the context of development, inflammation and circadian rhythms

Abstract

Macrophage subsets in tissue sites such as the peritoneal cavity are extremely heterogeneous in their phenotype and functions. These peritoneal macrophage subsets can be of dual origin: monocyte-derived or tissue-resident embryo-derived. Transcription factors are key to every step of the generation of both monocyte-derived and tissue resident embryo-derived macrophages. Retinoic-acid receptor-related orphan receptor alpha (Rora) is a transcription factor that has a role in a number of different processes within the body including cell development, inflammation and circadian rhythms. In terms of cell development it is known that Rora has a role in the development of immune cells ILC2s and Th17 cells. In this thesis the role that Rora has in the regulation of macrophage development, in particular in the development of monocyte-derived macrophages or tissue resident macrophages in the peritoneal cavity was investigated. Rora sg/sg mice contain a naturally occurring mutation in Rora and were used as to investigate Rora function in this thesis.