BAFF gene silencing attenuates allergic airway inflammation by promoting the generation of Tregs via activating pro-Treg cytokines

Abstract

Aims: Allergic airway inflammation is one of the major pathological events involved in asthma, and dysregulation of regulatory T cells (Treg) plays a crucial role in the development of allergic airway inflammation. Here, we attempted to investigate the regulatory effects of B cell-activating factor (BAFF) on Tregs in allergic airway inflammation.

Main methods: BAFF expression was analyzed by ELISA, quantitative reverse transcription PCR (RT-PCR) and Western blot assays. The levels of IL-4, TGF-β, IL-2, and IL-10 were tested using ELISA kits. Flow cytometry was conducted to analyze the populations of CTLA4⁺ Foxp3⁺ Tregs.

Key findings: BAFF was found to be aberrantly expressed in sputum and lungs in patients with asthma as well as OVA sensitized mice. BAFF silencing by lentiviral BAFF shRNA reduced the number of eosinophils and levels of IL-4 in the BAL fluid, as well as the Fizz1 expression in the lungs of OVA mice. Additionally, the population of CTLA4⁺ Foxp3⁺ Tregs were significantly decreased in OVA mice and had a negative correlation to BAFF levels in asthmatic patients and OVA mice. BAFF silencing in vivo increased levels of CTLA4⁺ Foxp3⁺ Tregs and the secretion of IL-10, and improved the regulatory phenotype and suppressor function of Tregs in vitro. Furthermore, BAFF can affect Tregs generation by regulating the production of the pro-Treg cytokines IL-2 and TGF-β.

Significance: BAFF has an inhibitory effect on the generation and suppressor function of Tregs by affecting pro-Tregs cytokines, thereby contributing to the development of allergic airway inflammation.

Keywords: Airway inflammation; Asthma; BAFF; IL-2; TGF-β; Treg.