Our lab is investigating mechanisms of regulation of immune responses and tissue homeostasis by the stromal microenvironment, with a particular focus on inflammatory/fibrotic diseases and cancer.
The stromal microenvironment is emerging as a novel and essential player in a number of human diseases characterized by overactivation or suppression of the immune system, including chronic inflammatory diseases, autoimmune diseases, and cancer. Our research on the stromal microenvironment aims at increasing our understanding of the underlying biological processes, an essential step toward the discovery of novel therapeutic approaches.
Stromal cells are non-hematopoietic cells that support the structure and function of all our organs. In lymphoid organs, specialized subsets of stromal cells play a pivotal role in immune responses by producing chemokines and growth factors, which organize lymphocytes migration and survival, as well as interaction with other immune subsets. Stromal cells therefore are essential for the homeostasis of the immune system. Additionally, stromal cells play key roles in several biological processes including vascular remodeling, tissue repair/regeneration and inflammation. Our lab is investigating the crosstalk of specific subsets of stromal cells with immune cells, endothelial cells and tissue stem cells, and exploring how perturbation of this fundamental stromal crosstalk impact on disease pathogenesis. Overall, our research aims at better understanding of the role of stromal cells in organ homeostasis and pathogenesis, in order to design better therapies in inflammatory diseases and cancer.
Our work has notably helped identifying an essential role for stromal perivascular progenitors in the scarring /fibrotic process, a major component of chronic inflammatory diseases and cancer. We further characterized the stromal niche for intestinal stem cells, which play a key role in maintaining stem cells and are involved in colitis. More recently, we identified an essential role for stromal maturation in the intestine in the first weeks after birth, when the intestine undergoes villus and vascular remodeling to fulfill nutrient requirement and enhance intestinal barrier function. Failure of such stromal maturation leads to decreased postnatal growth and dysregulated intestinal inflammatory/ repair responses (Dulauroy et al., Nature Medicine 2012; Stzepourginski et al., PNAS 2017; Di Carlo & Peduto, JCI 2018; Jacob et al., Cell Stem Cell 2022).
Using several experimental approaches, including cutting-edge lineage tracing and genetic depletion models, transcriptomics (single cell/bulk RNAseq) and high resolution cell imaging, we are now investigating the role of stromal cells in several organs, dissect mechanisms of regulation, and evaluate their impact on disease pathogenesis. Our research is currently focusing on the role of the stromal microenvironment on:
- Regulation of intestinal homeostasis and inflammation
- New mechanisms involved in tissue regeneration/repair and fibrosis
- Role of the stromal microenvironment in tumor immunity and immunotherapies
We are always looking for talented postdocs, PhD students or Master students with a strong interest in stroma-immune crosstalk. If you are interested in joining our team, please send your CV and cover letter to Lucie Peduto (pedutol@pasteur.fr)
