B lymphocyte-induced maturation protein 1 controls T_H9 cell development, IL-9 production, and allergic inflammation.

Abstract

The transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) has a key role in terminal differentiation in various T-cell subtypes. However, whether Blimp-1 regulates T_H9 differentiation and its role in allergic inflammation are unknown. We aimed to investigate the role of Blimp-1 in T_H9 differentiation and in the pathogenesis of allergic airway inflammation. In vitro T_H9 differentiation, flow cytometry, ELISA, and real-time PCR were used to investigate the effects of Blimp-1 on T_H9 polarization. T cell-specific Blimp-1-deficient mice, a model of allergic airway inflammation, and T-cell adoptive transfer to recombination-activating gene 1 (Rag-1)^-/- mice were used to address the role of Blimp-1 in the pathogenesis of allergic inflammation. We found that Blimp-1 regulates T_H9 differentiation because deleting Blimp-1 increased IL-9 production in CD4⁺ T cells in vitro. In addition, we showed that in T cell-specific Blimp-1-deficient mice, deletion of Blimp-1 in T cells worsened airway disease, and this worsening was inhibited by IL-9 neutralization. In asthmatic patients CD4⁺ T cells in response to TGF-β plus IL-4 increased IL-9 expression and downregulated Blimp-1 expression compared with expression in healthy control subjects. Blimp-1 overexpression in human T_H9 cells inhibited IL-9 expression. Blimp-1 is a pivotal negative regulator of T_H9 differentiation and controls allergic inflammation.