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International Immunology Advance Access originally published online on February 27, 2009
International Immunology 2009 21(4):467-476; doi:10.1093/intimm/dxp014
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

CXCL13 production by an established lymph node stromal cell line via lymphotoxin-beta receptor engagement involves the cooperation of multiple signaling pathways

Hidenori Suto1, Tomoya Katakai2, Manabu Sugai3, Tatsuo Kinashi2 and Akira Shimizu1,3

1 Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan
2 Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Moriguchi 570-8506, Japan
3 Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan

Correspondence to: T. Katakai; E-mail: katakait{at}takii.kmu.ac.jp

Non-hematopoietic mesenchymal stromal cells in secondary lymphoid organs play pivotal roles in tissue organization and immune responses by exhibiting specialized features such as the production of lymphoid homeostatic chemokines. However, the maturational process of stromal cells mediated by lymphotoxin-beta receptor (LTβR) signaling, a key for stromal maturation, remains unclear. Taking advantage of a stromal cell line established from mouse lymph node, which can produce a homeostatic chemokine, CXC chemokine ligand (CXCL) 13, by the engagement of LTβR but not by tumor necrosis factor (TNF) receptor (TNFR), we analyzed the details of intracellular signaling events during the maturational process. The activation of both canonical and non-canonical nuclear factor-{kappa}B (NF-{kappa}B) pathways was essential for CXCL13 induction; however, an excessive amount of non-canonical RelB–p52 complex was still insufficient for CXCL13 gene expression. Under RelB–p52-over-expressed conditions, TNF{alpha} could induce a markedly high amount of CXCL13 production, indicating that the downstream of TNFR contains an additional key component of signaling. We also found that protein kinase C activity plays a critical role in this process in addition to the NF-{kappa}B pathways. Taken together, it is suggested that the maturation of lymphoid stromal cells mediated by LTβR is accomplished by the cooperation of multiple signaling cascades.

Keywords: chemokine, NF-{kappa}B, protein kinase C, secondary lymphoid organ

Transmitting editor: T. Watanabe

Received 12 November 2008, accepted 27 January 2009.


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