The objective of the FLAMES team is to integrate stromal dynamics, inflammation and metabolism in the understanding of the loss of biological functions during aging to maintain and/or restore functional capacities. Our project aims to demonstrate that age-related chronic inflammation results from a defect of resolution of inflammation in tissues due to altered dialogue between macrophages and mesenchymal stromal cells (MSC).
This project is based on the use of innovative animal models, in vitro 4D strategies to reproduce tissue heterogeneity, as well as in silico approaches to study the inflammatory response and their effects on tissue repair.
The goal of our research project is to contribute to the identification of potential therapeutic targets to restore the dialogue between MSCs and macrophages to promote the development of a pro-resolutive response.
Mapping of Macrophages and MSC heterogeneity during physiological and pathophysiological aging
Our group are looking at the modification of the phenotype and of the modification of the functional capacities of macrophages and MSC during aging in human and in mice. This will be done by using confocal microscopy, flow cytometry and single cell transcriptomic approaches, as well as functional assays. In addition, as the macrophages heterogeneity relies also on their origin, the modification of the macrophage origin during aging are studying using lineage tracing and animal models of hematopoietic reconstruction.
Identify cellular and molecular targets that control the MSC/ Macrophages crosstalk during aging
Our group is characterizing the receptors and soluble factors involved in the interaction between MSC and macrophages and how this MSC-macrophage communication is modified during aging. We currently focus on CD54 as a key molecule in the cross-talk between Macrophages and MSCs (Esapgnolle et al) and on ecosanoids that play a central role in resolution of inflammation (ref).
The targets involved in MSC-macrophage interaction are studying using murine and human experimental models of vascularized 3D culture systems that combine different cellular actors
- endothelial cells
- immune cells
Strategies to restore the pro-resolutive macrophages through the re-education of macrophages or MSC/ Macrophages crosstalk
Our group is also developing different therapeutic approaches to reduce “inflammaging”. Pharmacological, nutritional approaches and also cell therapy approaches will be developed.
This research is carried out in collaboration with university partners and private companies.
Macrophages, hématopoïèse, régénération, vieillissement et tissu adipeux
Modélisation mathématique – prédiction – inflammation – régénération – vieillissement
Lea Da Costa
Macrophages, wound healing, collagen, resolution of inflammation, immunity
Macrophage polarization, infection and immunity, nuclear receptor, inflammation and its resolution
Hématopoïèse, tissu adipeux, Régénération, cytométrie
Cicatrisation – biomatériaux – thérapie cellulaire – macrophages – matrice 3D
Macrophages, Immunity, Microbiota, IBD, Aging
Cellules stromales mésenchymateuses, ingenierie cellulaire et tissulaire, organoides, bioréacteurs, culture 3D
Innate immunity/macrophages; mesenchymal stromal cells, cell-cell interaction, cell therapy, inflammation
Mesenchymal stromal cells, organoids, Biomaterials, 3D modelisation, stroma
Inflammaging, SASP, mesenchymal stromal cell and macrophage cross-talk, senescence
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- Espagnolle N, Balguerie A, Arnaud E, Sensebé L, Varin A. CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells. Stem Cell Reports. (2017), 8(4):961-976.
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- Rahabi M, Jacquemin G, Prat M, Meunier E, AlaEddine M, Bertrand B, Lefèvre L, Benmoussa K, Batigne P, Aubouy A, Auwerx J, Kirzin S, Bonnet D, Danjoux M, Pipy B, Alric L, Authier H, Coste A. Divergent Roles for Macrophage C-type Lectin Receptors, Dectin-1 and Mannose Receptors, in the Intestinal Inflammatory Response. Cell Rep. (2020), 30(13):4386-4398
- Prat M, Le Naour A, Coulson K, Lemée F, Leray H, Jacquemin G, Rahabi MC, Lemaitre L, Authier H, Ferron G, Barret JM, Martinez A, Ayyoub M, Delord JP, Gladieff L, Tabah-Fisch I, Prost JF, Couderc B, Coste A. Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression. J Immunother Cancer. (2020), 8(1):e000472