Your browser doesn't support javascript.
loading
A CTCF-binding site in the Mdm1-Il22-Ifng locus shapes cytokine expression profiles and plays a critical role in early Th1 cell fate specification.
Liu, Chunhong; Nagashima, Hiroyuki; Fernando, Nilisha; Bass, Victor; Gopalakrishnan, Jaanam; Signorella, Sadie; Montgomery, Will; Lim, Ai Ing; Harrison, Oliver; Reich, Lauren; Yao, Chen; Sun, Hong-Wei; Brooks, Stephen R; Jiang, Kan; Nagarajan, Vijayaraj; Zhao, Yongbing; Jung, Seolkyoung; Phillips, Rachael; Mikami, Yohei; Lareau, Caleb A; Kanno, Yuka; Jankovic, Dragana; Aryee, Martin J; Pekowska, Aleksandra; Belkaid, Yasmine; O'Shea, John; Shih, Han-Yu.
Afiliação
  • Liu C; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Nagashima H; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Fernando N; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Bass V; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gopalakrishnan J; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Signorella S; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, M
  • Montgomery W; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lim AI; Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Harrison O; Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Reich L; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yao C; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sun HW; Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Brooks SR; Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Jiang K; Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Nagarajan V; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhao Y; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Jung S; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Phillips R; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Mikami Y; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lareau CA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kanno Y; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Jankovic D; Immunoparasitology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Aryee MJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Pekowska A; Dioscuri Center of Chromatin Biology and Epigenomics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
  • Belkaid Y; Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • O'Shea J; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Shih HY; Neuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: han-yu.shih@nih.gov.
Immunity ; 57(5): 1005-1018.e7, 2024 May 14.
Article em En | MEDLINE | ID: mdl-38697116
ABSTRACT
Cytokine expression during T cell differentiation is a highly regulated process that involves long-range promoter-enhancer and CTCF-CTCF contacts at cytokine loci. Here, we investigated the impact of dynamic chromatin loop formation within the topologically associating domain (TAD) in regulating the expression of interferon gamma (IFN-γ) and interleukin-22 (IL-22); these cytokine loci are closely located in the genome and are associated with complex enhancer landscapes, which are selectively active in type 1 and type 3 lymphocytes. In situ Hi-C analyses revealed inducible TADs that insulated Ifng and Il22 enhancers during Th1 cell differentiation. Targeted deletion of a 17 bp boundary motif of these TADs imbalanced Th1- and Th17-associated immunity, both in vitro and in vivo, upon Toxoplasma gondii infection. In contrast, this boundary element was dispensable for cytokine regulation in natural killer cells. Our findings suggest that precise cytokine regulation relies on lineage- and developmental stage-specific interactions of 3D chromatin architectures and enhancer landscapes.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Interleucinas / Interferon gama / Células Th1 / Fator de Ligação a CCCTC / Interleucina 22 Limite: Animals Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Interleucinas / Interferon gama / Células Th1 / Fator de Ligação a CCCTC / Interleucina 22 Limite: Animals Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos