Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis.
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.
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Syogoin-Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan. khonda@virus.kyoto-u.ac.jp
K
K
Honda
H
H
Nakano
H
H
Yoshida
S
S
Nishikawa
P
P
Rennert
K
K
Ikuta
M
M
Tamechika
K
K
Yamaguchi
T
T
Fukumoto
T
T
Chiba
S I
SI
Nishikawa
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D054382:Chemokine CXCL13; D018925:Chemokines / Q000096:biosynthesis / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053259:Lymphotoxin beta Receptor; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000276:immunology; D010581:Peyer's Patches / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
C513179:CXCR5 protein, mouse; D015815:Cell Adhesion Molecules; D054382:Chemokine CXCL13; D018925:Chemokines; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; C505697:LTBR protein, human; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D018124:Receptors, Tumor Necrosis Factor; D019010:Vascular Cell Adhesion Molecule-1; C415350:interleukin-7 receptor, alpha chain; D018799:Intercellular Adhesion Molecule-1