Regulation of Peripheral Lymph Node Genesis by the Tumor Necrosis Factor Family Member Trance

نویسندگان

  • Dongku Kim
  • Reina E. Mebius
  • John D. MacMicking
  • Steffen Jung
  • Tom Cupedo
  • Yaneth Castellanos
  • Jaerang Rho
  • Brian R. Wong
  • Regis Josien
  • Nacksung Kim
  • Paul D. Rennert
  • Yongwon Choi
چکیده

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.

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عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 192  شماره 

صفحات  -

تاریخ انتشار 2000