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

• Published in: Journal of allergy and clinical immunology 2019-03, Vol.143 (3), p.1119
• Main Authors: Benevides, Luciana, Costa, Renata Sesti, Tavares, Lucas Alves, Russo, Momtchilo, Martins, Gislâine A, da Silva, Luis Lamberti P, Arruda, L Karla, Cunha, Fernando Q, Carregaro, Vanessa, Silva, João Santana
• Format: Article
• Language: English
• Subjects: Adoptive transfer; Allergic diseases; Animals; Asthma; Asthma - immunology; CD4 antigen; Cell Differentiation; Cell Line; Clonal deletion; Cytokines; Enzyme-linked immunosorbent assay; Flow cytometry; Glycerol; Humans; Hypersensitivity; Immunoglobulins; Inflammation; Inflammation - immunology; Interleukin 4; Interleukin 9; Interleukin-9 - genetics; Interleukin-9 - immunology; Laboratories; Lungs; Lymphocytes; Lymphocytes B; Lymphocytes T; Maturation; Medical research; Mice; Mice, Transgenic; Neutralization; Positive Regulatory Domain I-Binding Factor 1 - physiology; Proteins; RAG gene; Recombination; Respiratory tract; Respiratory tract diseases; T-Lymphocytes, Helper-Inducer - physiology; Transcription; Transcription factors
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2018.06.046

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 9 differentiation and its role in allergic inflammation are unknown. We aimed to investigate the role of Blimp-1 in T 9 differentiation and in the pathogenesis of allergic airway inflammation. In vitro T 9 differentiation, flow cytometry, ELISA, and real-time PCR were used to investigate the effects of Blimp-1 on T 9 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 9 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 9 cells inhibited IL-9 expression. Blimp-1 is a pivotal negative regulator of T 9 differentiation and controls allergic inflammation.