TNF superfamily member 13, APRIL, inhibits allergic lung inflammation

Authors:
Open Access
Publisher website
Google Scholar
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.

This publication has 26 references indexed in Scilit: