2020年6月19日，《免疫》杂志在线发表了法国艾克斯－马赛大学Marc Bajénoff课题组的最新成果。他们发现，表达转录因子WT1的网状成纤维细胞定义了维持和补充脾脏红髓巨噬细胞的基质微环境。

研究人员揭示了红髓巨噬细胞（RPM）动态平衡的机制，并专注于基质细胞的贡献，因为这些细胞在淋巴结和肝脏中执行固定和培育巨噬细胞的微环境功能。显微镜分析显示，RPM包裹在红髓成纤维细胞的网状结构中，其特征是转录因子WT1（Wilms’ Tumor 1）和集落刺激因子1（CSF1）的表达。

条件性敲除WT1⁺红髓成纤维细胞（而非白髓成纤维细胞）中的Csf1，能够在不改变循环CSF1水平的情况下，彻底改变了RPM网络。当RPM耗尽后，红髓成纤维细胞会短暂产生单核细胞趋化因子CCL2和CCL7，从而有助于RPM网络的补充。因此，红髓成纤维细胞固定并培养RPM，这一功能在人类中可能是保守的。

据了解，脾脏的RPM位于红髓索中，不断暴露于血流中来清除衰老的红血球（RBC）并从血红蛋白中回收铁。

附：英文原文

Title: Reticular Fibroblasts Expressing the Transcription Factor WT1 Define a Stromal Niche That Maintains and Replenishes Splenic Red Pulp Macrophages

Author: Alicia Bellomo, Isabelle Mondor, Lionel Spinelli, Marine Lagueyrie, Benjamin J. Stewart, Nicolas Brouilly, Bernard Malissen, Menna R. Clatworthy, Marc Bajénoff

Issue&Volume: 2020-06-19

Abstract: Located within red pulp cords, splenic red pulp macrophages (RPMs) are constantlyexposed to the blood flow, clearing senescent red blood cells (RBCs) and recyclingiron from hemoglobin. Here, we studied the mechanisms underlying RPM homeostasis,focusing on the involvement of stromal cells as these cells perform anchoring andnurturing macrophage niche functions in lymph nodes and liver. Microscopy revealedthat RPMs are embedded in a reticular meshwork of red pulp fibroblasts characterizedby the expression of the transcription factor Wilms’ Tumor 1 (WT1) and colony stimulatingfactor 1 (CSF1). Conditional deletion of Csf1 in WT1+ red pulp fibroblasts, but not white pulp fibroblasts, drastically altered the RPMnetwork without altering circulating CSF1 levels. Upon RPM depletion, red pulp fibroblaststransiently produced the monocyte chemoattractants CCL2 and CCL7, thereby contributingto the replenishment of the RPM network. Thus, red pulp fibroblasts anchor and nurtureRPM, a function likely conserved in humans.

DOI: 10.1016/j.immuni.2020.06.008

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30238-7