Ectopic Lymphoid-Organ Development Occurs through Interleukin 7-Mediated Enhanced Survival of Lymphoid-Tissue-Inducer Cells

Dominik Meier, Caroline Bornmann, Stephane Chappaz, Sandrine Schmutz, Luc A. Otten, Rhodri Ceredig, Hans Acha-Orbea, Daniela Finke

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148 Citations (Scopus)

Abstract

Development of Peyer's patches and lymph nodes requires the interaction between CD4+ CD3- IL-7Rα+ lymphoid-tissue inducer (LTi) and VCAM-1+ organizer cells. Here we showed that by promoting their survival, enhanced expression of interleukin-7 (IL-7) in transgenic mice resulted in accumulation of LTi cells. With increased IL-7 availability, de novo formation of VCAM-1+ Peyer's patch anlagen occurred along the entire fetal gut resulting in a 5-fold increase in Peyer's patch numbers. IL-7 overexpression also led to formation of multiple organized ectopic lymph nodes and cecal patches. After immunization, ectopic lymph nodes developed normal T cell-dependent B cell responses and germinal centers. Mice overexpressing IL-7 but lacking either RORγ, a factor required for LTi cell generation, or lymphotoxin α1β2 had neither Peyer's patches nor ectopic lymph nodes. Therefore, by controlling LTi cell numbers, IL-7 can regulate the formation of both normal and ectopic lymphoid organs.

Original languageEnglish
Pages (from-to)643-654
Number of pages12
JournalImmunity
Volume26
Issue number5
DOIs
Publication statusPublished - 25 May 2007
Externally publishedYes

Keywords

  • CELLIMMUNO
  • DEVBIO

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