Fibroblastic FLT3L supports lymph node dendritic cells in the interfollicular niche
Lane, R. S.; Wu, S. Z.; Davidson, C.; Byrne, A.; Kayser, B.; Huang, H.; Williams, K.; Fernandez, M.; Jiang, J.; Zhang, J.; Asuncion, R.; Decalf, J.; Roose-Girma, M.; Lee, W.; McGinnis, L.; Warming, S.; Stephenson, W.; Rost, S.; Moussion, C.; Biancalani, T.; Muller, S.; Turley, S. J.
Show abstract
Dendritic cell (DC) homeostasis is maintained in secondary lymphoid organs (SLOs) by Fms-like tyrosine kinase 3 ligand (FLT3L). The specific niche providing this DC growth factor within human and mouse SLOs is unclear. Here, we show that Gremlin1 (Grem1)-expressing lymph node fibroblastic reticular cells (FRCs) support DC homeostasis via provision of FLT3L. Grem1 FRCs co-localize with DCs and express FLT3L in human and mouse lymph nodes. Using a new genetic model, we provide evidence that FLT3L produced by GREM1 FRCs maintains lymph node preDCs, cDCs, and plasmacytoid DCs (pDCs). Spatial transcriptomics and cytofluorometry reveal that Grem1 FRC-derived FLT3L supports not only proliferation, but also survival of lymph node cDCs within the interfollicular zone (IFZ). Functionally, loss of Grem1 FRC-derived FLT3L impairs cDC priming of antigen-specific T cell responses. These findings provide key mechanistic insights underlying stromal cell support of DC homeostasis and function.
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