Stromal cells in intestinal homeostasis and immune responses

The immune system is composed of lymphoid and myeloid cells of hematopoietic origin that patrol the body for infection or injury. These immune mobile cells rely on signals produced by non-hematopoietic sessile cells, such as endothelial cells and a variety of ill-defined stromal cells including fibroblasts, perivascular cells and pericytes, to gain access to lymphoid tissues or injured/infected sites, and to form inflammatory aggregates. A distinct subset of stromal cells, called Lymphoid stromal (LS) cells, express structural chemokines, adhesion molecules and cytokines that are required to stabilize lymphoid tissues and play a central organizing role in the guidance and survival of leukocytes in lymphoid tissues. We have shown that LS cells are programmed during the fetal development of lymphoid tissues as well as in lymphocyte-rich organs such as the gut, and are re-induced by injury to organize lymphocyte recruitment in inflammatory lesions and tumors. They express the marker gp38 (podoplanin) and produce critical signals for leucocyte recruitment, survival and lymphangiogenesis. In the intestine, we have shown that CD34⁺ Gp38⁺ LS cells are an essential component of the intestinal epithelial stem cells (IESCs) niche at homeostasis, and contribute to intestinal inflammation after injury.

 

 

We are currently studying the cellular and molecular mechanisms that induce LS cells activation and expansion during inflammation and infection, as well as their crosstalk with immune cells, endothelial cells and parenchymal cells.