PMID- 30096391 OWN - NLM STAT- MEDLINE DCOM- 20200316 LR - 20210504 IS - 1097-6825 (Electronic) IS - 0091-6749 (Print) IS - 0091-6749 (Linking) VI - 143 IP - 3 DP - 2019 Mar TI - B lymphocyte-induced maturation protein 1 controls T(H)9 cell development, IL-9 production, and allergic inflammation. PG - 1119-1130.e3 LID - S0091-6749(18)31131-X [pii] LID - 10.1016/j.jaci.2018.06.046 [doi] AB - 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(+) 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. CI - Copyright (c) 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. FAU - Benevides, Luciana AU - Benevides L AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Costa, Renata Sesti AU - Costa RS AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Tavares, Lucas Alves AU - Tavares LA AD - Department of Cellular and Molecular Biology, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Russo, Momtchilo AU - Russo M AD - Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo. FAU - Martins, Gislaine A AU - Martins GA AD - F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute and Department of Medicine and Biomedical Science, Cedars-Sinai Medical Center (CSMC), Los Angeles, Calif. FAU - da Silva, Luis Lamberti P AU - da Silva LLP AD - Department of Cellular and Molecular Biology, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Arruda, L Karla AU - Arruda LK AD - Department of Clinical Medicine, Clinical Hospital of Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Cunha, Fernando Q AU - Cunha FQ AD - Department of Pharmacology, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Carregaro, Vanessa AU - Carregaro V AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Silva, Joao Santana AU - Silva JS AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil; Fiocruz-Bi-Institutional Translational Medicine Platform, Ribeirao Preto, Brazil. Electronic address: jsdsilva@fmrp.usp.br. LA - eng GR - R01 AI103542/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180807 PL - United States TA - J Allergy Clin Immunol JT - The Journal of allergy and clinical immunology JID - 1275002 RN - 0 (Interleukin-9) RN - EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1) SB - IM CIN - J Allergy Clin Immunol. 2019 Mar;143(3):937-939. PMID: 30193841 MH - Animals MH - Asthma/*immunology MH - *Cell Differentiation MH - Cell Line MH - Humans MH - Inflammation/immunology MH - Interleukin-9/genetics/*immunology MH - Mice, Transgenic MH - Positive Regulatory Domain I-Binding Factor 1/*physiology MH - T-Lymphocytes, Helper-Inducer/*physiology PMC - PMC8091629 MID - NIHMS1694653 OTO - NOTNLM OT - Allergy OT - Blimp-1 OT - IL-9 OT - T(H)9 differentiation COIS- Disclosure of potential conflict of interest: The authors have nothing disclose. EDAT- 2018/08/11 06:00 MHDA- 2020/03/17 06:00 PMCR- 2021/05/03 CRDT- 2018/08/11 06:00 PHST- 2017/11/16 00:00 [received] PHST- 2018/05/08 00:00 [revised] PHST- 2018/06/29 00:00 [accepted] PHST- 2018/08/11 06:00 [pubmed] PHST- 2020/03/17 06:00 [medline] PHST- 2018/08/11 06:00 [entrez] PHST- 2021/05/03 00:00 [pmc-release] AID - S0091-6749(18)31131-X [pii] AID - 10.1016/j.jaci.2018.06.046 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2019 Mar;143(3):1119-1130.e3. doi: 10.1016/j.jaci.2018.06.046. Epub 2018 Aug 7.