Summary
Besides their role as immune sentinels, macrophages fulfil specific functions that are strictly related to their tissue of residence. As an example, the loss of gut macrophages is correlated with impaired crypt cells differentiation which might favour the establishment of chronic intestinal inflammation. Macrophage functions are known to be regulated by tissular niches that imprint the macrophage tissue-specific identity. However, little is known about the “feedback” role of the macrophage for the maintenance and function of its niche. I hypothesise that the loss of a given macrophage subset might imperil its microenvironment through the alteration of its niche cells function or maintenance. Unravelling this feedback mechanism is technically challenging. Current mouse models target macrophages themselves, inducing their rapid replacement by circulating monocytes and thus preventing their long term depletion. Here, I will take advantage of their dependence to a continuous provision of trophic factors by their niche to manipulate and study gut macrophages in a novel manner. First, I will unravel the composition of each gut macrophage niches in a global and unbiased approach by combining single cells and spatial transcriptomics. Next, I will determine the potential cellular sources of trophic factors in each gut niches. Once identified, I will use specific mouse models to delete the trophic factor in the candidate cells to induce a long term depletion of a given macrophage subset. Finally, I will unravel the function of macrophages to their niche by analysing in silico the niche cells transcriptome after macrophage loss to highlight potential molecular interactions between the macrophage and the niche that would induce the survival or differentiation of niche cells. They would eventually be confirmed in vivo by using specific mouse models.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101030578 |
| Start date: | 01-09-2022 |
| End date: | 31-08-2024 |
| Total budget - Public funding: | 184 707,84 Euro - 184 707,00 Euro |
Cordis data
Original description
Besides their role as immune sentinels, macrophages fulfil specific functions that are strictly related to their tissue of residence. As an example, the loss of gut macrophages is correlated with impaired crypt cells differentiation which might favour the establishment of chronic intestinal inflammation. Macrophage functions are known to be regulated by tissular niches that imprint the macrophage tissue-specific identity. However, little is known about the “feedback” role of the macrophage for the maintenance and function of its niche. I hypothesise that the loss of a given macrophage subset might imperil its microenvironment through the alteration of its niche cells function or maintenance. Unravelling this feedback mechanism is technically challenging. Current mouse models target macrophages themselves, inducing their rapid replacement by circulating monocytes and thus preventing their long term depletion. Here, I will take advantage of their dependence to a continuous provision of trophic factors by their niche to manipulate and study gut macrophages in a novel manner. First, I will unravel the composition of each gut macrophage niches in a global and unbiased approach by combining single cells and spatial transcriptomics. Next, I will determine the potential cellular sources of trophic factors in each gut niches. Once identified, I will use specific mouse models to delete the trophic factor in the candidate cells to induce a long term depletion of a given macrophage subset. Finally, I will unravel the function of macrophages to their niche by analysing in silico the niche cells transcriptome after macrophage loss to highlight potential molecular interactions between the macrophage and the niche that would induce the survival or differentiation of niche cells. They would eventually be confirmed in vivo by using specific mouse models.Status
SIGNEDCall topic
MSCA-IF-2020Update Date
28-04-2024
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