A Distinct Subset of Fibroblastic Stromal Cells Constitutes the Cortex-Medulla Boundary Subcompartment of the Lymph Node.

A Distinct Subset of Fibroblastic Stromal Cells Constitutes the Cortex-Medulla Boundary Subcompartment of the Lymph Node.
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DOI:
10.3389/fimmu.2018.02196
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发表时间:
2018
影响因子:
7.3
通讯作者:
Katakai T
Katakai T
中科院分区:
医学2区
文献类型:
--
作者:
Takeuchi A;Ozawa M;Kanda Y;Kozai M;Ohigashi I;Kurosawa Y;Rahman MA;Kawamura T;Shichida Y;Umemoto E;Miyasaka M;Ludewig B;Takahama Y;Nagasawa T;Katakai T

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淋巴结(LN)免疫反应的时空调节依赖于其复杂的组织结构,由不同的成纤维细胞基质细胞(FSCs)支持的几个亚室组成。然而,对间质结构和相关的FSC亚群的复杂细节还没有完全了解。利用几只基因报告鼠,我们试图发现LN中未被识别的基质结构和FSCs。根据PDGFRβ、CCL21-Ser和CXCL12等报告基因的表达模式,明确区分了先前在大脑皮层中发现的四个FSC亚群。在这里,我们发现了一个独特的FSC亚群,在深皮质外周(DCP)同时表达CCL21-Ser和CXCL12,其特征是优先定位B细胞。这个亚群明显不同于CXCL12HighLepRHigh FSCs的延髓,后者含有浆细胞。DCP中B细胞的定位主要受CCL21-Ser控制,其次为CXCL12。此外,DCP和延髓的最佳发育需要B细胞。总之,我们的发现提示在皮质-髓质边界存在一个独特的微环境,并提供了LN内由不同FSC亚群构成的多层基质框架的高级视图。
The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRβ, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different from CXCL12highLepRhigh FSCs in the medullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN.
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