Nature immunology · 2025
Fibroblastic FLT3L supports lymph node dendritic cells in the interfollicular niche.
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Wu Sunny Z, Lane Ryan S, Davidson Christopher, Byrne Ashley, Protti Giulia, Marin Ines, Santosa Endi K, Guanieri Alberto, Kayser Brandon D, Huang Hejin, Williams Katherine, Fernandez Matthew, Jiang Jian, Zhang Juan, Asuncion Raymond, Vollmers Apple Cortez, Decalf Jérémie, Roose-Girma Merone, Lee Wyne P, McGinnis Lisa, Kapoor Varun N, Warming Soren, Stephenson William, Rost Sandra, Moussion Christine, Biancalani Tommaso, Müller Sören, Turley Shannon J
Аннотация
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.