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Hematopoietic/Mesenchymal Interaction in the Peyer's Patch Organogenesis
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Mice deficient in lymphotoxin β receptor (LTβR) or interleukin 7 receptor α (IL-7Rα) 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-7Rα + 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. lymphoid tissue lymphotoxin interleukin 7 chemokines chemotaxis Footnotes 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. Submitted: 9 October 2000 Revision requested 23 January 2001 Accepted: 31 January 2001
The Journal of Experimental Medicine – Rockefeller University Press
Published: Mar 5, 2001
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