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AhR Ligands Differentially Regulate miRNA-132 Which Targets HMGB1 and to Control the Differentiation of Tregs and Th-17 Cells During Delayed-Type Hypersensitivity Response.
Abdulla, Osama A; Neamah, Wurood; Sultan, Muthanna; Chatterjee, Saurabh; Singh, Narendra; Nagarkatti, Mitzi; Nagarkatti, Prakash.
Afiliação
  • Abdulla OA; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States.
  • Neamah W; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States.
  • Sultan M; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States.
  • Chatterjee S; Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States.
  • Singh N; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States.
  • Nagarkatti M; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States.
  • Nagarkatti P; Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United States.
Front Immunol ; 12: 635903, 2021.
Article em En | MEDLINE | ID: mdl-33679792
ABSTRACT
Aryl hydrocarbon receptor (AhR), is a transcription factor and an environmental sensor that has been shown to regulate T cell differentiation. Interestingly, AhR ligands exert varying effects from suppression to exacerbation of inflammation through induction of Tregs and Th-17 cells, respectively. In the current study, we investigated whether the differential effects of AhR ligands on T cell differentiation are mediated by miRNA during delayed-type hypersensitivity (DTH) reaction against methylated Bovine Serum Albumin (mBSA). Treatment of C57BL/6 mice with TCDD attenuated mBSA-mediated DTH response, induced Tregs, decreased Th-17 cells, and caused upregulation of miRNA-132. TCDD caused an increase in several Treg subsets including inducible peripheral, natural thymic, and Th3 cells. Also, TCDD increased TGF-ß and Foxp3 expression. In contrast, treating mice with FICZ exacerbated the DTH response, induced inflammatory Th17 cells, induced IL-17, and RORγ. Analysis of miRNA profiles from draining lymph nodes showed that miR-132 was upregulated in the TCDD group and downregulated in the FICZ group. Transfection studies revealed that miRNA-132 targeted High Mobility Group Box 1 (HMGB1). Downregulation of HMGB1 caused an increase in FoxP3+ Treg differentiation and suppression of Th-17 cells while upregulation of HMGB1 caused opposite effects. Moreover, TCDD was less effective in suppressing DTH response and induction of Tregs in mice that were deficient in miR-132. In summary, this study demonstrates that TCDD and FICZ have divergent effects on DTH response and T cell differentiation, which is mediated through, at least in part, regulation of miRNA-132 that targets HMGB1.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carbazóis / Diferenciação Celular / Linfócitos T Reguladores / Receptores de Hidrocarboneto Arílico / Proteína HMGB1 / MicroRNAs / Fatores de Transcrição Hélice-Alça-Hélice Básicos / Células Th17 / Dibenzodioxinas Policloradas / Hipersensibilidade Tardia Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carbazóis / Diferenciação Celular / Linfócitos T Reguladores / Receptores de Hidrocarboneto Arílico / Proteína HMGB1 / MicroRNAs / Fatores de Transcrição Hélice-Alça-Hélice Básicos / Células Th17 / Dibenzodioxinas Policloradas / Hipersensibilidade Tardia Idioma: En Ano de publicação: 2021 Tipo de documento: Article