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FLAMES

Agnès Coste-Borthwick

FLAMES : INFLAMMAGING CONTROL BY DYNAMIC MSC / MYELOID CELL CROSSTALK

Team Flame

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.

 

research axis

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).

Cellules
Interaction entre les cellules stromales mesenchymateuses (vert) et les macrophages (violet) via le CD54 (jaune) in vitro (image de gauche) et in vivo (image de droite). Crédit: A.Varin-C.Barreau
Interaction between mesenchymal stromal cells (green) and macrophages (purple) through CD54 (yellow) in vitro (left) and in adipose tissue (right). Photo credit: A.Varin-C.Barreau

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
Communication between multiple spheroids generated from MSC after 8 days in a hydrogel »
Scanning electron microscopy image of a self-organized MSC network in a biomaterial pore after 15 days of culture in a perfused bioreactor

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.

team members

Macrophages, hématopoïèse, régénération, vieillissement et tissu adipeux 

Adèle Arlat2

Adéle Arlat

PhD students
Agnès Coste 2

Agnès Coste

Group leader MCU-UT3 Pharmacy
Benedicte Bertrand2

Benedicte Bertrand

Technical assistant-UT3 Pharmacy
Clément blot 2

Clément Blot

PhD students
Godefroy Jacquemin 2

Godefroy Jacquemin

PhD students
Jean-Gérard Descamps 2

Jean-Gérard Descamps

Technician-EFS
Kim Coulson 2

Kimberley Coulson

PhD students

Modélisation mathématique – prédiction – inflammation – régénération – vieillissement

Lea Da Costa 2

Lea Da Costa

PhD students

Macrophages, wound healing, collagen, resolution of inflammation, immunity

Marie Salon 2

Marie Salon

PhD students
Lise Lefévre

Lise Lefèvre

MCU-UT3 Pharmacy

Macrophage polarization, infection and immunity, nuclear receptor, inflammation and its resolution

Hélène Authier

Hélène Authier

MCU-UT3 Pharmacy

Hématopoïèse, tissu adipeux, Régénération, cytométrie

Marie-Laure Renoud 2

Marie-Laure Renoud

Engineer Assistant-INSERM

Cicatrisation – biomatériaux – thérapie cellulaire – macrophages – matrice 3D

Maylis Farno 2

Maylis Farno

Post-doctoral fellows

Macrophages, Immunity, Microbiota, IBD, Aging

Mouna Rahabi 2

Mouna Rahabi

Post-doctoral fellows
Mélissa Parny done

Mélissa Parny

Post-doctoral fellows

Cellules stromales mésenchymateuses, ingenierie cellulaire et tissulaire, organoides, bioréacteurs, culture 3D

Mélanie_Gadelorge

Mélanie Gadelorge

Engineer-EFS
Béatrice cousin

Béatrice Cousin

Co-group leader DR - CNRS

Innate immunity/macrophages; mesenchymal stromal cells, cell-cell interaction, cell therapy, inflammation

Audrey Varin

Audrey Varin

CR-EFS
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Khaddouj Benmoussa

Post-doctoral fellows

Mesenchymal stromal cells, organoids, Biomaterials, 3D modelisation, stroma

Nicolas Espagnolle

Nicolas Espagnolle

CR-EFS
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Judith Fillaux

MCU-PH-UT3 Medicine
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Sophie Cassaing

MCU-PH-UT3 Medicine
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Marianne Dutour

Technicienne
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Brigitte Sallerin

PU-PH

Inflammaging, SASP, mesenchymal stromal cell and macrophage cross-talk, senescence

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Victorine Douin-Echinard

MCU-UT3 Pharmacy
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Laurent Alric

PU-PH-UT3 Medicine
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Bernard Pipy

DR émérite Inserm
Publications
Team Partners
scientific partners
financial supports