美国基因泰克公司Shannon J. Turley团队取得一项新突破。他们的最新研究揭示了成纤维细胞源性FLT3L维持滤泡间区淋巴结树突状细胞。这一研究成果发表在2025年11月17日出版的国际学术期刊《自然—免疫学》上。

本研究表明，表达Gremlin1（GREM1）的淋巴结成纤维网状细胞（FRCs）通过提供FLT3L支持DC稳态。表达Grem1的FRCs与DCs共定位，并在人和非主题淋巴结中表达FLT3LG/Flt3l。利用一个新的遗传模型，该研究团队提供了由GREM1⁺ FRCs产生的FLT3L维持淋巴结DC前体（preDCs）和常规（cDCs）和浆细胞样DC （pDCs）的证据。空间转录组学和细胞荧光学显示GREM1⁺FRCs衍生的FLT3L不仅支持增殖，还支持滤泡间区（IFZ）内淋巴结preDCs和cDCs的存活。功能上，GREM1⁺FRCs衍生的FLT3L损害cDC对免疫和感染的抗原特异性T细胞反应的激活。这些发现为基质细胞支持DC稳态和功能提供了关键的机制见解。

据介绍，树突状细胞（DC）稳态是由Fms样酪氨酸激酶3配体（FLT3L）维持的。提供这种DC生长因子的特定生态位在人类和非主题SLOs中尚不清楚。

附：英文原文

Title: Fibroblastic FLT3L supports lymph node dendritic cells in the interfollicular niche

Author: 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, Jrmie, Roose-Girma, Merone, Lee, Wyne P., McGinnis, Lisa, Kapoor, Varun N., Warming, Soren, Stephenson, William, Rost, Sandra, Moussion, Christine, Biancalani, Tommaso, Mller, Sren, Turley, Shannon J.

Issue&Volume: 2025-11-17

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-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.

DOI: 10.1038/s41590-025-02332-2

Source: https://www.nature.com/articles/s41590-025-02332-2