CXCL13 production by an established lymph node stromal cell line via lymphotoxin-beta receptor engagement involves the cooperation of multiple signaling pathways.
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 (LTbetaR) 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 LTbetaR 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-kappaB (NF-kappaB) 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, TNFalpha 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-kappaB pathways. Taken together, it is suggested that the maturation of lymphoid stromal cells mediated by LTbetaR is accomplished by the cooperation of multiple signaling cascades.
Suto
Hidenori
H
Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Katakai
Tomoya
T
Sugai
Manabu
M
Kinashi
Tatsuo
T
Shimizu
Akira
A
D000818:Animals; D002460:Cell Line; D054382:Chemokine CXCL13 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D014409:Tumor Necrosis Factor-alpha; D051841:Transcription Factor RelB; D011493:Protein Kinase C