Embryonic FAP+ lymphoid tissue organizer cells generate the reticular network of adult lymph nodes
Embryonic FAP+ lymphoid tissue organizer cells generate the reticular network of adult lymph nodes
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DOI：
10.1084/jem.20181705
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发表时间：
2019-10-01
影响因子：
15.3
通讯作者：
Fearon, Douglas T.
中科院分区：
文献类型：
--
作者：
Denton, Alice E.;Carr, Edward J.;Fearon, Douglas T.
获得性免疫的诱导依赖于LN的结构组织，而LN的结构组织又由支撑LN结构的基质细胞控制。使用一种新的命运映射小鼠模型，我们追踪间充质LN基质细胞（mLNSCs）的发育起源到以前未描述的胚胎成纤维细胞活化蛋白-α（FAP）（+）祖细胞。LN原基的FAP（+）细胞表达β-光敏素受体（LT β R）和血管细胞粘附分子（VCAM），但不表达细胞间粘附分子（ICAM），提示它们是早期间充质淋巴组织形成细胞（mLTo）。克隆标记显示FAP（+）祖细胞局部分化为mLNSCs。这一过程也在非淋巴组织中对感染作出反应，以促进三级淋巴结构的发育，从而模仿LN对感染作出反应的个体发育过程。
The induction of adaptive immunity is dependent on the structural organization of LNs, which is in turn governed by the stromal cells that underpin LN architecture. Using a novel fate-mapping mouse model, we trace the developmental origin of mesenchymal LN stromal cells (mLNSCs) to a previously undescribed embryonic fibroblast activation protein-alpha (FAP)(+) progenitor. FAP(+) cells of the LN anlagen express lymphotoxin beta receptor (LT beta R) and vascular cell adhesion molecule (VCAM), but not intercellular adhesion molecule (ICAM), suggesting they are early mesenchymal lymphoid tissue organizer (mLTo) cells. Clonal labeling shows that FAP(+) progenitors locally differentiate into mLNSCs. This process is also coopted in nonlymphoid tissues in response to infection to facilitate the development of tertiary lymphoid structures, thereby mimicking the process of LN ontogeny in response to infection.