On-chip human lymph node stromal network for evaluating dendritic cell and T-cell trafficking

The lymph node paracortex, also known as the T-cell zone, consists of a network of fibroblastic reticular cells (FRCs) that secrete chemokines to induce T-cell and dendritic cell trafficking into the paracortex. To model the lymph node paracortex, we utilized multi-channel microfluidic devices to engineer a 3D lymph node stromal network from human cultured FRCs embedded in a collagen I-fibrin hydrogel. In the hydrogel, the FRCs self-assembled into an interconnected network, secreted the extracellular matrix proteins entactin, collagen IV, and fibronectin, as well as expressed an array of immune cell trafficking chemokines. Although the engineered FRC network did not secrete characteristic CCR7-ligand chemokines (i.e. CCL19 and CCL21), human primary TNF- matured monocyte-derived dendritic cells, CD45RA+ T-cells, and CD45RA- T-cells migrated toward the lymph node stromal network to a greater extent than toward a blank hydrogel. Furthermore, the FRCs co-recruited dendritic cells and antigen-specific T-cells into the lymph node stromal network. This engineered lymph node stromal network may help evaluate how human dendritic cells and T-cells migrate into the lymph node paracortex via CCR7-independent mechanisms.