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FLAMES
Agnès Coste-Borthwick
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.
AXIS 1
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.
AXIS 2
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
- stroma

AXIS 3
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.
- Luche E, Robert V, Cuminetti V, Pomié C, Sastourné-Arrey Q, Waget A, Arnaud E, Varin A, Labit E, Laharrague P, Burcelin R, Casteilla L, Cousin B. Corrupted adipose tissue endogenous myelopoiesis initiates diet-induced metabolic disease. Elife. (2017) 28;6.
- 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.
- Martini H, Iacovoni JS, Maggiorani D, Dutaur M, Marsal DJ, Roncalli J, Itier R, Dambrin C, Pizzinat N, Mialet-Perez J, Cussac D, Parini A, Lefevre L, Douin-Echinard V. Aging induces cardiac mesenchymal stromal cell senescence and promotes endothelial cell fate of the CD90 + subset. Aging Cell. (2019), 18(5):e13015.
- Lefèvre L, Authier H, Stein S, Majorel C, Couderc B, Dardenne C, Eddine MA, Meunier E, Bernad J, Valentin A, Pipy B,Schoonjans K, Coste A. LRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPAR ligand synthesis. Nat Commun. (2015), 6:6801.
- Alaeddine M, Prat M, Poinsot V, Gouazé-Andersson V, Authier H, Meunier E, Lefèvre L, Alric C, Dardenne C, Bernad J, Alric L, Segui B, Balard P, Couderc F, Couderc B, Pipy B, Coste A. IL13-Mediated Dectin-1 and Mannose Receptor Overexpression Promotes Macrophage Antitumor Activities through Recognition of Sialylated Tumor Cells. Cancer Immunol Res. (2019),7(2):321-334
- 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
- Brevet N°2854078 Use of PPARgamma agonists as anti-infective agents.
- Brevet N° 2984719 A method of analysing the progress of wound healing at both macroscopic and microscopic levels;
- Brevet N° 2984722 Non-invasive device for collecting exudates from a wound, its use and kit comprising said device
- Brevet N° 1262644 Use of acetylsalicylic acid for the prevention and/or treatment of diabetic wounds
- Brevet N° FR1750280 and international extension in 2019 “Immunomodulatory effects of P17 peptide
- Brevet FR1663344 TLR4-specific antagonist for the treatment of multiple myeloma