Your browser doesn't support javascript.
loading
Macrophage inflammatory and regenerative response periodicity is programmed by cell cycle and chromatin state.
Daniel, Bence; Belk, Julia A; Meier, Stefanie L; Chen, Andy Y; Sandor, Katalin; Czimmerer, Zsolt; Varga, Zsofia; Bene, Krisztian; Buquicchio, Frank A; Qi, Yanyan; Kitano, Hugo; Wheeler, Joshua R; Foster, Deshka S; Januszyk, Michael; Longaker, Michael T; Chang, Howard Y; Satpathy, Ansuman T.
Afiliação
  • Daniel B; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA. Electronic address: bdaniel8@stanford.edu.
  • Belk JA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Meier SL; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Chen AY; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Sandor K; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Czimmerer Z; Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen 4032, Hungary; Institute of Genetics, Biological Research Centre, Eötvös Loránd Research Network, Szeged 6726, Hungary.
  • Varga Z; Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen 4032, Hungary.
  • Bene K; Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen 4032, Hungary.
  • Buquicchio FA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Qi Y; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Kitano H; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
  • Wheeler JR; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Foster DS; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Januszyk M; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Longaker MT; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA 94305, USA; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanf
  • Chang HY; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: howchang@stanford.edu.
  • Satpathy AT; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA; Program in Immunology, Stanford University, Stanford, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA. Electronic addr
Mol Cell ; 83(1): 121-138.e7, 2023 01 05.
Article em En | MEDLINE | ID: mdl-36521490
ABSTRACT
Cell cycle (CC) facilitates cell division via robust, cyclical gene expression. Protective immunity requires the expansion of pathogen-responsive cell types, but whether CC confers unique gene expression programs that direct the subsequent immunological response remains unclear. Here, we demonstrate that single macrophages (MFs) adopt different plasticity states in CC, which leads to heterogeneous cytokine-induced polarization, priming, and repolarization programs. Specifically, MF plasticity to interferon gamma (IFNG) is substantially reduced during S-G2/M, whereas interleukin 4 (IL-4) induces S-G2/M-biased gene expression, mediated by CC-biased enhancers. Additionally, IL-4 polarization shifts the CC-phase distribution of MFs toward the G2/M phase, providing a subpopulation-specific mechanism for IL-4-induced, dampened IFNG responsiveness. Finally, we demonstrate CC-dependent MF responses in murine and human disease settings in vivo, including Th2-driven airway inflammation and pulmonary fibrosis, where MFs express an S-G2/M-biased tissue remodeling gene program. Therefore, MF inflammatory and regenerative responses are gated by CC in a cyclical, phase-dependent manner.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Interleucina-4 Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Interleucina-4 Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article