Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE

D Kim, R E Mebius, J D MacMicking, S Jung, T Cupedo, Y Castellanos, J Rho, B R Wong, R Josien, N Kim, P D Rennert, Y Choi

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Proper lymph node (LN) development requires tumor necrosis factor-related activation-induced cytokine (TRANCE) expression. Here we demonstrate that the defective LN development in TRANCE(-/)- mice correlates with a significant reduction in lymphotoxin (LT)alphabeta(+)alpha(4)beta(7)(+)CD45(+)CD4(+)CD3(-) cells and their failure to form clusters in rudimentary mesenteric LNs. Transgenic TRANCE overexpression in TRANCE(-/)- mice results in selective restoration of this cell population into clusters, and results in full LN development. Transgenic TRANCE-mediated restoration of LN development requires LTalphabeta expression on CD45(+) CD4(+)CD3(-) cells, as LNs could not be induced in LTalpha(-/)- mice. LTalpha(-/)- mice also showed defects in the fate of CD45(+)CD4(+)CD3(-) cells similar to TRANCE(-/)- mice. Thus, we propose that both TRANCE and LTalphabeta regulate the colonization and cluster formation by CD45(+) CD4(+)CD3(-) cells in developing LNs, the degree of which appears to correlate with the state of LN organogenesis.

Original languageEnglish
Pages (from-to)1467-78
Number of pages12
JournalJournal of Experimental Medicine
Volume192
Issue number10
Publication statusPublished - 20 Nov 2000

Cite this

Kim, D., Mebius, R. E., MacMicking, J. D., Jung, S., Cupedo, T., Castellanos, Y., ... Choi, Y. (2000). Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE. Journal of Experimental Medicine, 192(10), 1467-78.