Fibroblastic FLT3L supports lymph node dendritic cells in the interfollicular niche

Sunny Z. Wu; Ryan S. Lane; Christopher Davidson; Ashley Byrne; Giulia Protti; Inés Marín; Endi K. Santosa; Alberto Guarnieri; Brandon D. Kayser; Hejin Huang; Katherine Williams; Matthew Fernandez; Jian Wei Jiang; Juan Zhang; Raymond Asuncion; Apple Cortez Vollmers; Jérémie Decalf; Merone Roose‐Girma; Wyne P. Lee; Lisa M. McGinnis; Varun N. Kapoor; Søren Warming; William Stephenson; Sandra Rost; Christine Moussion; Tommaso Biancalani; Sören Müller; Shannon J. Turley

doi:10.1038/s41590-025-02332-2

ImmunologyNature ImmunologyNov 17, 2025

Peer-reviewed journal article

Fibroblastic FLT3L supports lymph node dendritic cells in the interfollicular niche

Sunny Z. Wu iD, Ryan S. Lane iD, Christopher Davidson, Ashley Byrne iD, Giulia Protti iD, Inés Marín iD, Endi K. Santosa iD, Alberto Guarnieri iD, Brandon D. Kayser iD, Hejin Huang iD, Katherine Williams iD, Matthew Fernandez, Jian Wei Jiang iD, Juan Zhang iD, Raymond Asuncion, Apple Cortez Vollmers iD, Jérémie Decalf iD, Merone Roose‐Girma iD, Wyne P. Lee iD, Lisa M. McGinnis iD, Varun N. Kapoor iD, Søren Warming iD, William Stephenson iD, Sandra Rost iD, Christine Moussion iD, , Shannon J. Turley iD

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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.