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 language | English (US) |
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Pages (from-to) | 164-171 |
Number of pages | 8 |
Journal | European Journal of Immunology |
Volume | 41 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2011 |
Externally published | Yes |
Keywords
- Asthma
- IL-13
- IL-4
- Immune response
- Th2 transcription
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy