Active stromal cells

Stromal cells in immunity

Stromal cells, including epithelial, endothelial and mesenchymal cells, play a central organizing role in the guidance and survival of leukocytes in lymphoid or inflamed tissues. In the intestine for example, epithelial cells translate and transfer information on the commensal microbiota from the lumen to the internal stromal cells and leukocytes, and orchestrate early activation steps of the immune system. Lymphoid stromal (LS) cells express structural chemokines, adhesion molecules and cytokines that are required to stabilize lymphoid tissues, and are generated early during the fetal development of lymphoid tissues, and are re-induced during inflammation. During chronic inflammation, such LS cells organize the formation of tertiary lymphoid tissues that aggravate disease. They express the marker gp38 (also termed podoplanin), as well as other marker co-expressed by a subset of activated fibroblasts, the myofibroblasts.




The generation of lymphoid stromal cells during ontogeny, inflammation and tumor progression. Lymph node anlagen were imaged at E16.5; LTi cells are in green. Inflammation is shown in the ear 3 days after injection of Complete Freund's Adjuvant. A pancreatic tumor is shown in 12 weeks old RIP-Tag mice. Gp38 is expressed by lymphoid stromal cells and Lyve1 by lymphatic endothelial cells (Peduto et al., J. Immunol., 2009).


Activated stromal cells, in particular LS cells, are organizers of immunity. However, chronic activation of stromal cells can also lead to the development of pathologies, through the generation of tertiary lymphoid tissues in inflammatory disease or the production of excessive extracellular matrix in fibrosis. In tumors, the cancer cell to stroma crosstalk generates a postive feedback loop that favors tumor progression.




Activated stoma cells organize the development of immunity. However, chronic activation of stromal cells leads to inflammatory disease through the generation of tertiary lymphoid tissues, fibrotic diseases and cancer.


Distinct subsets of stromal cells can be identified using cell surface markers, such as gp38 (podoplanin), ICAM-1 and VCAM-1. We are generating BAC (bacterial artificial chromosome)-transgenic GFP-reporter mice to visualize stromal cells expressing particular chemokines, cytokines, cytokine receptors or matrix metalloproteases. The transgenes we use also allow for the fate mapping of stromal cell subsets and their specific ablation in vivo.

   

BAC-transgenic mice reporting the expression of chemokines in Peyer's patches (left) and small intestine (center and right). Costains are: left, B220 (red) and Lyve-1 (blue), center and right, gp38 (red) and nuclei (blue).