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

Author(s)

Benevides, Luciana ^[1] ; Costa, Renata Sesti ^[1] ; Tavares, Lucas Alves ^[2] ; Russo, Momtchilo ^[3] ; Martins, Gislaine A. ^{[4, 5]} ; da Silva, Luis Lamberti P. ^[2] ; Karla Arruda, L. ^[6] ; Cunha, Fernando Q. ^[7] ; Carregaro, Vanessa ^[1] ; Silva, Joao Santana ^{[1, 8]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cellular & Mol Biol, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[4] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 - USA

^[5] Cedars Sinai Med Ctr, Dept Med & Biomed Sci, Los Angeles, CA 90048 - USA

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Clin Hosp, Dept Clin Med, Ribeirao Preto - Brazil

^[7] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[8] Fiocruz Bi Inst Translat Med Platform, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: Journal of Allergy and Clinical Immunology; v. 143, n. 3, p. 1119+, MAR 2019.
• Web of Science Citations: 5

Abstract

Background: 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(H)9 differentiation and its role in allergic inflammation are unknown. Objective: We aimed to investigate the role of Blimp-1 in T(H)9 differentiation and in the pathogenesis of allergic airway inflammation. Methods: In vitro T(H)9 differentiation, flow cytometry, ELISA, and real-time PCR were used to investigate the effects of Blimp-1 on T(H)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. Results: We found that Blimp-1 regulates T(H)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(+)1 T cells in response to TGF-beta 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(H)9 cells inhibited IL-9 expression. Conclusion: Blimp-1 is a pivotal negative regulator of T(H)9 differentiation and controls allergic inflammation. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC