Fibroblastic FLT3L supports lymph node dendritic cells in the interfollicular niche.

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-expressing FRCs colocalize with DCs and express FLT3LG/Flt3l in human and mouse lymph nodes. Using a new genetic model, we provide evidence that FLT3L produced by GREM1+ FRCs maintains lymph node DC precursors (preDCs) and both conventional (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 preDCs and cDCs within the interfollicular zone (IFZ). Functionally, loss of GREM1+ FRC-derived FLT3L impairs cDC activation of antigen-specific T cell responses to both immunization and infection. These findings provide key mechanistic insights underlying stromal cell support of DC homeostasis and function.