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The developmental origins of macrophages define their metabolic and inflammatory properties
The developmental origins of macrophages define their metabolic and inflammatory properties
It is established that tissue resident macrophages have mixed developmental origins in most organs. They derive in variable extent from yolk sac (YS) hematopoiesis during embryonic development. Bone marrow (BM) hematopoietic progenitors give rise to tissue macrophages in postnatal life, and their contribution increases upon organ injury. Tissue resident macrophages are in perpetual interplay with their surroundings; thus, they are continuously reprogrammed by the microenvironment of their tissue of residence in order to serve immunologic and tissue specific functions. However, in tissue where macrophages are programmed to keep tissue homeostasis and other tissue specialized features, gene expression profiling and epigenetic landscape data revealed that heterogeneity among macrophage population exists, a property that could be attributed to distinct cells origin. Nevertheless, whether YS- and BM-derived macrophages functional properties and their contributions in their tissue of residence homeostasis or in the event microbial or inflammatory challenge varies, still remains to be shown and represents a significant question with major clinical importance. In order to decipher cell-intrinsic macrophage programs that are independent of the tissue environment, we immortalized hematopoietic progenitors from YS and BM using conditional homeobox protein Hox-B8 (Hoxb8) and carried out an in-depth functional and molecular analysis of differentiated macrophages. While YS and BM macrophages demonstrate close similarities in cellular growth, differentiation, phagocytic properties, migration velocity and their susceptibility to cell death inducers they display differences in cell metabolism, expression of inflammatory markers, and inflammasome activation. Thus, macrophage ontogeny is associated with distinct cellular programs and immune response.
macrophages, yolk sac, Bone marrow, inflammasome
Elhag, Sara Rahamatalla Mohamed
2022
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Elhag, Sara Rahamatalla Mohamed (2022): The developmental origins of macrophages define their metabolic and inflammatory properties. Dissertation, LMU München: Faculty of Medicine
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Abstract

It is established that tissue resident macrophages have mixed developmental origins in most organs. They derive in variable extent from yolk sac (YS) hematopoiesis during embryonic development. Bone marrow (BM) hematopoietic progenitors give rise to tissue macrophages in postnatal life, and their contribution increases upon organ injury. Tissue resident macrophages are in perpetual interplay with their surroundings; thus, they are continuously reprogrammed by the microenvironment of their tissue of residence in order to serve immunologic and tissue specific functions. However, in tissue where macrophages are programmed to keep tissue homeostasis and other tissue specialized features, gene expression profiling and epigenetic landscape data revealed that heterogeneity among macrophage population exists, a property that could be attributed to distinct cells origin. Nevertheless, whether YS- and BM-derived macrophages functional properties and their contributions in their tissue of residence homeostasis or in the event microbial or inflammatory challenge varies, still remains to be shown and represents a significant question with major clinical importance. In order to decipher cell-intrinsic macrophage programs that are independent of the tissue environment, we immortalized hematopoietic progenitors from YS and BM using conditional homeobox protein Hox-B8 (Hoxb8) and carried out an in-depth functional and molecular analysis of differentiated macrophages. While YS and BM macrophages demonstrate close similarities in cellular growth, differentiation, phagocytic properties, migration velocity and their susceptibility to cell death inducers they display differences in cell metabolism, expression of inflammatory markers, and inflammasome activation. Thus, macrophage ontogeny is associated with distinct cellular programs and immune response.