RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation.

  • Wang G
  • Yu Y
  • Sun C
 et al. 
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Abstract

Although the role of the T(H)1 and T(H)17 subsets of helper T cells as disease mediators in autoimmune neuroinflammation remains a subject of some debate, none of their signature cytokines are essential for disease development. Here we report that interleukin 23 (IL-23) and the transcription factor RORγt drove expression of the cytokine GM-CSF in helper T cells, whereas IL-12, interferon-γ (IFN-γ) and IL-27 acted as negative regulators. Autoreactive helper T cells specifically lacking GM-CSF failed to initiate neuroinflammation despite expression of IL-17A or IFN-γ, whereas GM-CSF secretion by Ifng(-/-)Il17a(-/-) helper T cells was sufficient to induce experimental autoimmune encephalomyelitis (EAE). During the disease effector phase, GM-CSF sustained neuroinflammation via myeloid cells that infiltrated the central nervous system. Thus, in contrast to all other known helper T cell-derived cytokines, GM-CSF serves a nonredundant function in the initiation of autoimmune inflammation regardless of helper T cell polarization.

Author-supplied keywords

  • 2015
  • ???? T cells and autoimmunity
  • AMP-Activated Protein Kinases/immunology
  • Animals
  • Antibodies
  • Antibodies: therapeutic use
  • Antigen
  • Autoimmune
  • Autoimmune Diseases
  • Autoimmune Diseases: immunology
  • Autoimmune Diseases: metabolism
  • Autoimmune Diseases: pathology
  • Autoimmune Diseases: therapy
  • Autoimmune diseases
  • Autoimmunity
  • Autoimmunity: immunology
  • CD8-Positive T-Lymphocytes/*immunology/metabolism
  • Cell Differentiation
  • Cell Differentiation/*immunology
  • Cell Differentiation: genetics
  • Cell Differentiation: immunology
  • Cellimmuno
  • Cells
  • Cultured
  • Cytokines
  • Cytokines: immunology
  • Encephalomyelitis
  • Epithelial Cells
  • Epithelial Cells: immunology
  • Experimental
  • Experimental: chemi
  • Experimental: immun
  • Experimental: metab
  • Experimental: patho
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Genetic
  • Genetic: immunology
  • Glycolysis
  • Glycoproteins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor:
  • Group F
  • HeLa Cells
  • Helper-Inducer
  • Helper-Inducer/*immunology/metaboli
  • Helper-Inducer: immunology
  • Helper-Inducer: metabolism
  • Hep G2 Cells
  • Humans
  • Hypoxia-Inducible Factor 1
  • Imiquimod
  • Immunity
  • Immunologic Memory/immunology
  • Inbred C57BL
  • Inbred Strains
  • Interferon-gamma
  • Interferon-gamma: genetics
  • Interferon-gamma: immunology
  • Interferon-gamma: pharmacology
  • Interleukin-12
  • Interleukin-12: pharmacology
  • Interleukin-17
  • Interleukin-17: genetics
  • Interleukin-17: immunology
  • Interleukin-23
  • Interleukin-23: genetics
  • Interleukin-23: immunology
  • Interleukin-23: pharmacology
  • Interleukins
  • Interleukins: pharmacology
  • Jurkat Cells
  • Knockout
  • Lymphocyte Activation
  • Lymphocyte Activation/*immunology
  • Lymphocyte Activation: immunology
  • Lymphocyte Subsets
  • Lymphocyte Subsets: immunology
  • Lymphocyte Subsets: metabolism
  • Male
  • Member 3
  • Member 3: biosynthesis
  • Member 3: g
  • Member 3: genetics
  • Member 3: i
  • Member 3: m
  • Member 3: metabolism
  • Messenger
  • Messenger: biosynthesis
  • Mice
  • Molimmuno
  • Myelin-Oligodendrocyte Glycoprotein
  • Negative regulation
  • Neoplasms
  • Neoplasms: genetics
  • Neoplasms: immunology
  • Nuclear Receptor Subfamily 1
  • Peptide Fragments
  • Phophatases
  • Pneumonia
  • Pneumonia: immunology
  • Pneumonia: metabolism
  • Pneumonia: pathology
  • Promoter Regions
  • Proto-Oncogene Proteins c-myc/immunology
  • RNA
  • ROR ??
  • RORγt
  • Receptors
  • Regulatory/*immunology/metabolism
  • STAT Transcription Factors
  • STAT Transcription Factors: genetics
  • STAT Transcription Factors: immunology
  • STAT3 Transcription Factor
  • STAT3 Transcription Factor: deficiency
  • STAT3 Transcription Factor: genetics
  • STAT3 Transcription Factor: immunology
  • STAT3 Transcription Factor: metabolism
  • STAT5 Transcription Factor
  • STAT5 Transcription Factor: genetics
  • STAT5 Transcription Factor: immunology
  • STATs
  • Signal Transduction
  • Signal Transduction/immunology
  • Signal Transduction: immunology
  • Sysbio
  • T helper type 17
  • T-Cell/immunology
  • T-Lymphocytes
  • T-cell lymphoma
  • TOR Serine-Threonine Kinases/immunology
  • Th1 Cells
  • Th1 Cells: drug effects
  • Th1 Cells: immunology
  • Th1 Cells: metabolism
  • Th17 Cells
  • Th17 Cells: drug effects
  • Th17 Cells: immunology
  • Th17 Cells: metabolism
  • Th17 cells
  • Tight Junctions
  • Tight Junctions: immunology
  • Transcription
  • Transgenic
  • Truncated STATs
  • Upstream Stimulatory Factors
  • Upstream Stimulatory Factors: physiology
  • alpha Subunit/immunolo
  • bloodjournal
  • epigenetic
  • for personal use only
  • gene regulation
  • june 9
  • m www
  • org by guest on
  • stats
  • t-helper cell
  • transcription factors

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Authors

  • G Wang

  • Y Yu

  • C Sun

  • T Liu

  • T Liang

  • L Zhan

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