TNF superfamily member 13, APRIL, inhibits allergic lung inflammation

Yanping Xiao, Seiichi Motomura, Vadim Deyev, Eckhard R. Podack

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The T-cell functions of a proliferation-inducing ligand (APRIL, also known as TNFSF13) remain largely undefined. We previously showed that APRIL suppressed Th2 cytokine production in cultured CD4+ T cells and Th2 antibody responses. Here we show that APRIL suppresses allergic lung inflammation, which is associated with diminished expression of the transcription factor c-maf. Mice deficient in the April gene (April-/- mice) had significantly aggravated lung inflammation compared with WT mice in the ovalbumin-induced allergic lung inflammation model. Likewise, blockade of APRIL in WT mice by the APRIL-receptor fusion protein, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)-Ig, enhanced lung inflammation. Transfer of APRIL-sufficient, ovalbumin-specific, TCR-transgenic CD4+ T (OT-II) cells to April-/- mice restored the suppressive effect of APRIL on lung inflammation. Mechanistically, the expression of the Th2 cytokine transcription factor c-maf, but not GATA-3, was markedly enhanced in April-/- CD4+ T cells at the RNA and protein level and under non-polarizing (Th neutral, ThN) and Th2-polarizing conditions. Since c-maf transactivates the IL-4 gene, the increased c-maf expression in April-/- mice readily explains increased Th2 cytokine production. Independent of its effect on IL-4, APRIL suppressed IL-13 expression. APRIL thus may regulate lung inflammation in a dual way, by acting on c-maf expression and by directly controlling IL-13 production.

Original languageEnglish (US)
Pages (from-to)164-171
Number of pages8
JournalEuropean Journal of Immunology
Volume41
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Asthma
  • IL-13
  • IL-4
  • Immune response
  • Th2 transcription

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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