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<p>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 <i>FLT3LG/Flt3l</i> in human and mouse lymph nodes. Using a new genetic model, we provide evidence that FLT3L produced by GREM1<sup>+</sup> FRCs maintains lymph node DC precursors (preDCs) and both conventional (cDCs) and plasmacytoid DCs (pDCs). Spatial transcriptomics and cytofluorometry reveal that GREM1<sup>+</sup> 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<sup>+</sup> 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.</p>

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Fibroblastic FLT3L supports lymph node dendritic cells in the interfollicular niche

  • 期刊论文

  • 发表日期：

    2025年11月17日

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

摘要

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.