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Distinct Activities of Stromal Cells Involved in the Organogenesis of Lymph Nodes and Peyer’s Patches¹

Masato Okuda^*,, Atsushi Togawa^*, Hiromi Wada and Shin-ichi Nishikawa^2,*

^* Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan; and Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan

It is now well established that the interaction between "inducer" cells of hemopoietic origin and "organizer" cells of mesenchymal lineage is involved in the organogenesis of lymph node (LN) and Peyer’s patch (PP). Organizer cells are defined by the expression of VCAM-1 and ICAM-1 and the production of homeostatic chemokines. However, several studies suggested the presence of a diversity among these cells from different lymphoid tissues. Thus, we attempted to define the difference of organizer cells of LN and PP in terms of gene expression profile. Microarray analyses of organizer cells revealed that these cells isolated from embryonic mesenteric LN expressed higher levels of genes that are related to inflammation, tissue remodeling, and development of mesenchymal lineage compared with those from PP. Several transcription factors related to epithelial-mesenchymal interactions were also up-regulated in organizer cells from LN. These results indicate that organizer cells in LN and PP are indeed distinct and suggest that the organizer cells in LN are at a more activated stage than those in PP.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (to A.T. and S.N.).

² Address correspondence and reprint requests to Dr. Shin-ichi Nishikawa, Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. E-mail address: nishikawa{at}cdb.riken.jp

³ Abbreviations used in this paper: PLT, peripheral lymphoid tissue; LN, lymph node; MLN, mesenteric LN; PP, Peyer’s patch; DP, double positive; RANK, receptor activator for NF-B; RANKL, RANK ligand; LT, lymphotoxin; E17.5, embryonic day 17.5; P4, postnatal day 4.

⁴ The online version of this article contains supplemental material.