Blimp-1 controls Th9 cell development, IL-9 production and allergic inflammation

Publication date: Available online 7 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Luciana Benevides, Renata Sesti Costa, Lucas Alves Tavares, Momtchilo Russo, Gislâine A. Martins, Luis Lamberti P. da Silva, Luiza Karla de P. Arruda, Fernando Q. Cunha, Vanessa Carregaro, João Santana Silva

Abstract

Background

The transcriptional repressor Blimp-1 has a key role in terminal differentiation in various T cell subtypes. However, whether Blimp-1 regulates Th9 differentiation and its role in allergic inflammation are unknown.

Objective

We aimed to investigate the role of Blimp-1 in Th9 differentiation and in the pathogenesis of allergic airway inflammation.

Methods

In vitro Th9 differentiation, flow cytometry, ELISA and real-time PCR were used to investigate the effects of Blimp-1 on Th9 polarization. T cell-specific Blimp-1-deficient mice (CKO), a model of allergic airway inflammation, and T cell adoptive transfer to Rag-1^-/- mice were used to address the role of Blimp-1 in the pathogenesis of allergic inflammation.

Results

We found that Blimp-1 regulates Th9 differentiation, as deleting Blimp-1 increased IL-9 production in CD4⁺ T cells in vitro. In addition, we showed that in CKO mice, deletion of Blimp-1 in T cells worsened airway disease, and this worsening was inhibited by the neutralization of IL-9. In asthmatic patients, CD4⁺ T cells in response to TGF-β plus IL-4 increased IL-9 expression and down-regulated Blimp-1 expression compared to those of healthy controls. Blimp-1 overexpression in human Th9 cells inhibited IL-9 expression. Conclusion: Blimp-1 is a pivotal negative regulator of Th9 differentiation and controls allergic inflammation.

Graphical abstract

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