Functional responses of lymphoid stromal cells to Toll-like receptor stimuli

Introduction: Lymphoid stromal cells control the spatial organization of lymphoid tissues and respond dynamically during immune reactions, undergoing transcriptional and phenotypic changes that can influence immune responses. The exogenous signals to which lymphoid stromal cells respond, and how, are still being defined. Methods: Lymphoid stromal cells express Toll-like receptors (TLRs), but it has been difficult to separate the role of the stromal cell response to TLR ligands from that of immune cells. To understand this better, we established a method to culture primary lymphoid stromal cells to study their behaviour Results: We found that co-culturing fibroblasts with lymphatic endothelial cells produced the most stable cultures, in contrast to pure fibroblast cultures. Lymphoid stromal cells directly sensed TLR ligands, upregulating the cell adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in response to TLR3 and TLR4 stimulation. Lymphoid stromal cells also secreted cytokines and chemokines in response to TLR4 ligation. Conclusion: Lymphoid stromal cells can respond directly to pathogen- and damage-associated molecules, potentially modulating the immunological outcome.