Lezing 'Dissecting the identity, functions and molecular regulation of mononuclear phagocyte subsets in mouse and human'
Marc Dalod (Centre d'Immunologie de Marseille-Luminy, France) will present his latest work on mononuclear phagocyte subsets.
Abstract: Our goal is to advance our understanding of the identity, functions and molecular regulation of mononuclear phagocyte (MP) subsets, at steady state as well as under conditions of infections by intracellular pathogens or of cancer development. We designed and use a systems biology strategy combining various approaches including i) comparative genomics to identify the similarities between MP subsets across tissues and vertebrate species, ii) bioinformatics analyses of conserved genes to identify networks of signalling pathways and transcription factors involved in the specification of MP subset ontogeny and functions, iii) development and study of innovative mouse models engineered to specifically lack MP subsets, or lose expression of candidate genes selectively in these cells, and iv) extension to humans of the studies performed in mice. We focus on plasmacytoid dendritic cells (pDC), XCR1+ classical DC (cDC) and cells derived from circulating classical monocytes (cMo). It is not clear what the extent of the physiological functions of pDC, XCR1+ cDC and cMo-derived cells are in vivo, how redundant these functions may be between these different MP subsets or with other cell types, and how they are regulated including for polarization towards immunity versus tolerance. In contrast to XCR1+ cDC which might be rather prone for the induction and maintenance of protective immune responses against intracellular pathogens and tumours, depending on the disease stage pDC and cMo-derived cells could be either immuno-activating and protective or immunosuppressive and deleterious. Hence, it is crucial to better understand how the protective versus deleterious functions of these cells are regulated, in order to design novel immunotherapeutic strategies to reprogram the MP system for promoting health over disease during infections or cancer.