Published online 5 March 2001.
© The Rockefeller University Press, 0022-1007/2001/3/621/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 5, March 5, 2001 621-630
Molecular Basis for Hematopoietic/Mesenchymal Interaction during Initiation of Peyer's Patch Organogenesis
Kenya Hondaa,b,
Hiroyasu Nakanod,e,
Hisahiro Yoshidaa,
Satomi Nishikawaa,
Paul Rennertf,
Koichi Ikutac,
Masakatsu Tamechikae,
Kazuhito Yamaguchih,
Tetsuo Fukumotog,
Tsutomu Chibab, and
Shin-Ichi Nishikawaa
a Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
b Department of Gastroenterology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
c Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
d Department of Immunology, Juntendo University, School of Medicine, Tokyo 113-8421, Japan
e Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
f Department of Immunology, Biogen, Incorporated, Cambridge, Massachusetts 02142
g Department of Anatomy, Yamaguchi University School of Medicine, Ube 755-8505, Japan
h Institute of Laboratory Animals, Yamaguchi University School of Medicine, Ube 755-8505, Japan
the Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Syogoin-Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan.81-75-751-416981-75-751-4161
khonda{at}virus.kyoto-u.ac.jp
Mice deficient in lymphotoxin β receptor (LTβR) or interleukin 7 receptor 
(IL-7R) 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-7R+ 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 LTβR to express adhesion molecules and chemokines. Thus, promotion of PP development relies on mutual interaction between mesenchymal and lymphoid cells.
Key Words: lymphoid tissue • lymphotoxin • interleukin 7 • chemokines • chemotaxis
Abbreviations used in this paper: BLC, B lymphocyte chemoattractant; CCR, CC chemokine receptor; CXCR, CXC chemokine receptor; E, embryonic day; ELC, EBV-induced molecule 1 ligand chemokine; FDC, follicular dendritic cell; ICAM, intercellular adhesion molecule; LT, lymphotoxin; MAdCAM, mucosal addressin cell adhesion molecule; PDGFR, platelet-derived growth factor receptor; PP, Peyer's patch; RT, reverse transcription; Spl, spleen; SLC, secondary lymphoid organ chemokine; VCAM, vascular cell adhesion molecule.
© 2001 The Rockefeller University Press
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