Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P, Ikuta K, Tamechika M, Yamaguchi K, Fukumoto T, Chiba T, Nishikawa S I
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Syogoin-Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.
J Exp Med. 2001 Mar 5;193(5):621-30. doi: 10.1084/jem.193.5.621.
Mice deficient in lymphotoxin beta receptor (LTbetaR) or interleukin 7 receptor alpha (IL-7Ralpha) lack Peyer's patches (PPs). Deficiency in CXC chemokine receptor 5 (CXCR5) also severely affects the development of PPs. A molecular network involving these three signaling pathways has been implicated in PP organogenesis, but it remains unclear how they are connected during this process. We have shown that PP organogenesis is initiated at sites containing IL-7Ralpha(+) lymphoid cells and vascular cell adhesion molecule (VCAM)-1/intercellular adhesion molecule (ICAM)-1 expressing nonlymphoid elements. Here we characterize these lymphoid and nonlymphoid components in terms of chemokine signals. The lymphoid population expresses CXCR5 and has a strong chemotactic response to B lymphocyte chemoattractant (BLC). Importantly, chemokines produced by VCAM-1(+)ICAM-1(+) nonlymphoid cells mediate the recruitment of lymphoid cells. Furthermore, we show that these VCAM-1(+)ICAM-1(+) cells are mesenchymal cells that are activated by lymphoid cells through the LTbetaR to express adhesion molecules and chemokines. Thus, promotion of PP development relies on mutual interaction between mesenchymal and lymphoid cells.
缺乏淋巴毒素β受体（LTβR）或白细胞介素7受体α（IL-7Rα）的小鼠没有派尔集合淋巴结（PPs）。CXC趋化因子受体5（CXCR5）的缺乏也严重影响PPs的发育。一个涉及这三种信号通路的分子网络与PPs的器官发生有关，但在此过程中它们是如何连接的仍不清楚。我们已经表明，PPs的器官发生起始于含有IL-7Rα(+)淋巴细胞和表达血管细胞黏附分子（VCAM）-1/细胞间黏附分子（ICAM）-1的非淋巴细胞成分的部位。在此，我们根据趋化因子信号对这些淋巴细胞和非淋巴细胞成分进行了表征。淋巴细胞群体表达CXCR5，并对B淋巴细胞趋化因子（BLC）有强烈的趋化反应。重要的是，由VCAM-1(+)ICAM-1(+)非淋巴细胞产生的趋化因子介导了淋巴细胞的募集。此外，我们表明这些VCAM-1(+)ICAM-1(+)细胞是间充质细胞，它们通过LTβR被淋巴细胞激活，从而表达黏附分子和趋化因子。因此，PPs发育的促进依赖于间充质细胞和淋巴细胞之间的相互作用。
