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A Non-Classical Ontogenetic Path Gives Rise to a GM-CSF Dependent Macrophage Population in the Developing Salivary Gland


Westermann, Frederike. A Non-Classical Ontogenetic Path Gives Rise to a GM-CSF Dependent Macrophage Population in the Developing Salivary Gland. 2024, University of Zurich, Faculty of Science.

Abstract

The cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) has obtained a lot of attention for its role in inflammatory conditions, while its role in developmental and steady state myelopoiesis, beyond alveolar macrophages in the lung, remains incompletely understood. In this thesis, we identified GM-CSF to be crucial for the development and maintenance of a macrophage subset in the salivary gland (SG). Macrophages make up the predominant part of the immune compartment in the SG, but their origin and functional repertoire are not well understood. Recently, phenotypic changes of the tissue resident macrophages have been shown to occur over the course of postnatal maturation. We discovered a yet undescribed CD226-expressing subset of tissue resident macrophages in the SG that expands throughout postnatal development (GM-MACS). Using high-dimensional spectral flow-cytometry and our Fate-map and reporter of GM-CSF (FROGxAi14) mouse strain, we observed active GM-CSF production in the SG correlating with the emergence of GM-MACS and identified group 2 innate lymphoid cells (ILC2s) as main source of GM-CSF in the developing SG. Lineage-tracing revealed that GM-MACS originate from fetal monocytes in a perinatal wave and are later expanded postnatally by bone marrow Ly6C+ monocyte-dendritic cell progenitors (MDPs). Their ontogeny distinguishes them from other macrophages and highlights similarities to DC3s. We found GM-MACS to be highly phagocytic and capable antigen presenting cells, while they appear to be dispensable for tissue maturation and development. Their functional properties indicate a role in inflammation or protective immune responses. Altogether, our study enhanced our knowledge on the SG macrophage profile. Macrophage diversity and heterogeneity indicate divers roles for macrophages in the SG at different developmental states.

Abstract

The cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) has obtained a lot of attention for its role in inflammatory conditions, while its role in developmental and steady state myelopoiesis, beyond alveolar macrophages in the lung, remains incompletely understood. In this thesis, we identified GM-CSF to be crucial for the development and maintenance of a macrophage subset in the salivary gland (SG). Macrophages make up the predominant part of the immune compartment in the SG, but their origin and functional repertoire are not well understood. Recently, phenotypic changes of the tissue resident macrophages have been shown to occur over the course of postnatal maturation. We discovered a yet undescribed CD226-expressing subset of tissue resident macrophages in the SG that expands throughout postnatal development (GM-MACS). Using high-dimensional spectral flow-cytometry and our Fate-map and reporter of GM-CSF (FROGxAi14) mouse strain, we observed active GM-CSF production in the SG correlating with the emergence of GM-MACS and identified group 2 innate lymphoid cells (ILC2s) as main source of GM-CSF in the developing SG. Lineage-tracing revealed that GM-MACS originate from fetal monocytes in a perinatal wave and are later expanded postnatally by bone marrow Ly6C+ monocyte-dendritic cell progenitors (MDPs). Their ontogeny distinguishes them from other macrophages and highlights similarities to DC3s. We found GM-MACS to be highly phagocytic and capable antigen presenting cells, while they appear to be dispensable for tissue maturation and development. Their functional properties indicate a role in inflammation or protective immune responses. Altogether, our study enhanced our knowledge on the SG macrophage profile. Macrophage diversity and heterogeneity indicate divers roles for macrophages in the SG at different developmental states.

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Additional indexing

Item Type:Dissertation (monographical)
Referees:Becher Burkhard, Greter Melanie, Tugues Solsona Sonia, Ginhoux Florent
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
UZH Dissertations
Dewey Decimal Classification:610 Medicine & health
570 Life sciences; biology
Language:English
Place of Publication:Zürich
Date:26 March 2024
Deposited On:26 Mar 2024 13:59
Last Modified:26 Mar 2024 14:00
Number of Pages:128
OA Status:Closed