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 and are essential 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. We, and others, have notably shown that specific stromal progenitors wrapped around vessels have an essential role in the scarring/fibrotic process, a major component of chronic diseases (Dulauroy, Nature medicine 2012). We have also shown that a subset of intestinal stromal cells form a specialized microenvironment around intestinal crypts, providing paracrine signals to maintain intestinal stem cells and playing a role in the developement of colitis (Stzepourginski, PNAS 2017). To further investigate the mechanisms underlying tissue repair, we are using several experimental approaches, including cutting-edge lineage tracing and genetic depletion models for stromal subsets, cell imaging and transcriptomics, in different models of acute and chronic injury affecting the skin, lung, intestine or muscle.
Our research is currently focusing on:
- Defining the role of lymphoid stromal cells in intestinal homeostasis and lymphoid organs
- Identifying perivascular stromal progenitors with roles in fibrosis and tissue regeneration
- Deciphering the stromal crosstalk to tumor cells and impact on tumor immunity and anti-cancer therapies