Your browser doesn't support javascript.
loading
Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses.
Lee, Jihyung; Zhang, Junyan; Chung, Young-Jun; Kim, Jun Hwan; Kook, Chae Min; González-Navajas, José M; Herdman, David S; Nürnberg, Bernd; Insel, Paul A; Corr, Maripat; Mo, Ji-Hun; Tao, Ailin; Yasuda, Kei; Rifkin, Ian R; Broide, David H; Sciammas, Roger; Webster, Nicholas Jg; Raz, Eyal.
Afiliação
  • Lee J; Department of Medicine, University of California San Diego, San Diego, United States.
  • Zhang J; Department of Medicine, University of California San Diego, San Diego, United States.
  • Chung YJ; The Second Affiliated Hospital of Guangzhou Medical University (GMU), The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou, China.
  • Kim JH; Center for Immunology, Inflammation and Immune-mediated disease, GMU, Guangzhou, China.
  • Kook CM; Department of Medicine, University of California San Diego, San Diego, United States.
  • González-Navajas JM; Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Chungnam, Republic of Korea.
  • Herdman DS; Department of Medicine, University of California San Diego, San Diego, United States.
  • Nürnberg B; Department of Medicine, University of California San Diego, San Diego, United States.
  • Insel PA; Center for Immunology, Inflammation and Immune-mediated disease, GMU, Guangzhou, China.
  • Corr M; Alicante Institute for Health and Biomedical Research (ISABIAL - FISABIO), Alicante, Spain.
  • Mo JH; Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, Madrid, Spain.
  • Tao A; Department of Medicine, University of California San Diego, San Diego, United States.
  • Yasuda K; Department of Pharmacology and Experimental Therapy, University of Tübingen, Tübingen, Germany.
  • Rifkin IR; Department of Medicine, University of California San Diego, San Diego, United States.
  • Broide DH; Department of Pharmacology, University of California San Diego, San Diego, United States.
  • Sciammas R; Department of Medicine, University of California San Diego, San Diego, United States.
  • Webster NJ; Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Chungnam, Republic of Korea.
  • Raz E; The Second Affiliated Hospital of Guangzhou Medical University (GMU), The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou, China.
Elife ; 92020 02 04.
Article em En | MEDLINE | ID: mdl-32014112
Cyclic AMP (cAMP) is involved in many biological processes but little is known regarding its role in shaping immunity. Here we show that cAMP-PKA-CREB signaling (a pattern recognition receptor [PRR]-independent mechanism) regulates conventional type-2 Dendritic Cells (cDC2s) in mice and reprograms their Th17-inducing properties via repression of IRF4 and KLF4, transcription factors essential for cDC2-mediated Th2 induction. In mice, genetic loss of IRF4 phenocopies the effects of cAMP on Th17 induction and restoration of IRF4 prevents the cAMP effect. Moreover, curdlan, a PRR-dependent microbial product, activates CREB and represses IRF4 and KLF4, resulting in a pro-Th17 phenotype of cDC2s. These in vitro and in vivo results define a novel signaling pathway by which cDC2s display plasticity and provide a new molecular basis for the classification of novel cDC2 and cDC17 subsets. The findings also reveal that repressing IRF4 and KLF4 pathway can be harnessed for immuno-regulation.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Células Th2 / Fatores Reguladores de Interferon / Receptores de Reconhecimento de Padrão / Células Th17 Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Células Th2 / Fatores Reguladores de Interferon / Receptores de Reconhecimento de Padrão / Células Th17 Idioma: En Ano de publicação: 2020 Tipo de documento: Article