Th2 Cells in Health and Disease

Nakayama, Toshinori; Hirahara, Kiyoshi; Onodera, Atsushi; Endo, Yusuke; Hosokawa, Hiroyuki; Shinoda, Kenta; Tumes, Damon J.; Okamoto, Yoshitaka

doi:10.1146/annurev-immunol-051116-052350

Cited by 303 publications

(278 citation statements)

References 217 publications

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“…The detailed mechanisms underlying the GATA3-dependent regulation of its target genes are described in Section 5. [3,[43][44][45][46]. PcG and TrxG proteins were originally identiied in Drosophila; however, they also play essential roles in controlling mammalian gene expression in various normal and tumor tissues.…”

Section: Gata3 Plays Roles In Various Tissues As Well As the Immune Smentioning

confidence: 99%

“…This study showed that a binding patern in which Ezh2 binds upstream and Menin binds downstream of the transcription start site was frequently found at highly expressed genes, and a binding patern in which Ezh2 and Menin bind to opposite positions was frequently found at low-expressed genes in T lymphocytes. Interestingly, genes showing a binding patern in which Ezh2 and Menin occupied the same position displayed greatly enhanced sensitivity to Ezh2 deletion [3,58].…”

Section: Spatial Interplay Between Polycomb and Trithorax Complexesmentioning

confidence: 99%

“…Epigenetic changes at the Gata3 gene locus in T cells are essential for the acquisition and maintenance of the Th2 cell identity [3,51,59]. During Th2 cell diferentiation, PcG and TrxG proteins dynamically change their binding paterns at the Gata3 gene locus.…”

Section: The Gata3 Gene Is Epigenetically Regulated During Th2 Cell Dmentioning

confidence: 99%

“…However, the responses caused by these subsets are sometimes excessive and result in immunological diseases. For example, an excess amount of Th2 cytokines is known to induce allergic disease, such as asthma [3].…”

Section: Introductionmentioning

confidence: 99%

“…In fact, GATA3 or Menin deletion results in the loss of Th2 identity [10,11]. Clarifying the interplay between the transcription factors and epigenetic modiiers is required to comprehend the Th2 cell biology and to identify new therapeutic targets for Th2-mediated immunological diseases [3].…”

Section: Introductionmentioning

confidence: 99%

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The Interplay between Transcription Factors and Epigenetic Modifications in Th2 Cells

Onodera¹,

Kokubo²,

Nakayama³

2018

Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects

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Functionally polarized CD4 T helper (Th) cells, such as Th1, Th2, and Th17 cells, are essential for the regulation of acquired immunity. Diferentiation of naïve CD4 T cells into Th2 cells is characterized by chromatin remodeling and the induced expression of a set of Th2-speciic genes, which include Th2 cytokine genes. In the irst stage of this differentiation, a Th2-skewing cytokine environment, especially IL-4, induces STAT6 activation. Activated STAT6 increases the expression of GATA3, a master regulator of Th2 cell diferentiation, via direct binding to the Gata3 gene locus. This transcriptional induction of Gata3 mRNA during Th2 cell diferentiation is accompanied by dynamic changes in the binding paterns of two epigenetic modiication proteins such as Polycomb and Trithorax complexes. Consequently, expressed GATA3 epigenetically modiies and upregulates Th2-speciic genes to establish Th2 cell identity. This identity is maintained by high-level expression of the Gata3 gene controlled by Menin, which is a member of the Trithorax proteins, after cycles of cultivation in vitro and a long-term resting state in vivo. Thus, the Menin-GATA3 axis handles the Th2-speciic gene regulatory network.

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Section: Gata3 Plays Roles In Various Tissues As Well As the Immune Smentioning

confidence: 99%

Section: Spatial Interplay Between Polycomb and Trithorax Complexesmentioning

confidence: 99%

Section: The Gata3 Gene Is Epigenetically Regulated During Th2 Cell Dmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Interplay between Transcription Factors and Epigenetic Modifications in Th2 Cells

Onodera¹,

Kokubo²,

Nakayama³

2018

Gene Expression and Regulation in Mammalian Cells - Transcription From General Aspects

Self Cite

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Pro‐Regenerative Glycopeptide Hydrogel Activates Type 2 Immune Response for Wound Healing via Macrophage‐T Cell Crosstalk

Wang,

Liu,

Wang

et al. 2024

Adv Funct Materials

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Immunomodulatory biomaterials are increasingly used in regenerative medicine. Biomimetic glycopeptide hydrogel is found to accelerate cutaneous wound healing by inducing macrophage M2‐type polarization, however, it is unclear whether this will possibly orchestrate a pro‐regenerative T cell immunity. Here the aim of this study is to elucidate the reparative T‐cell immune response in tissue regeneration by augmenting macrophage‐T cell crosstalk with a novel immunomodulatory glycopeptide hydrogel (termed as GRKgel) self‐assembled by mannose receptor‐binding glucomannan (GM) chemically grafted with RADA16‐conjugated T‐cell epitope. The glycopeptide can be phagocytized and processed by macrophages, which then presents peptides to naïve T cells and polarizes them into T helper 2 (TH2) cells through IL‐4‐dependent STAT6/GATA3 or c‐Maf pathways. Strikingly, full‐thickness skin wound repair in mice indicates a superior efficacy of GRKgel on restoring the pathological structure and hair follicle by provoking TH2 immune response, increasing the residence of M2 macrophages, as well as promoting angiogenesis at the local tissue environment. Furthermore, genomics results illustrates the role of GRKgel serving as an immunomodulatory niche, orchestrating immune cell crosstalk and promoting extracellular matrix (ECM) reconstruction. Collectively, this study highlights the significance of crosstalk between immune cells in evoking pro‐healing T‐cell immunity, providing a promising drug‐/cytokine‐free strategy for endogenous tissue regeneration.

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Shaping the diversity of Th2 cell responses in epithelial tissues and its potential for allergy treatment

Matthias

Zielinski

2019

Eur J Immunol

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Th2 cells have evolved to protect from large helminth infections and to exert tissue protective functions in response to nonmicrobial noxious stimuli. The initiation, maintenance, and execution of these functions depend on the integration of diverse polarizing cues by cellular sensors and molecular programs as well as the collaboration with cells that are coopted for signal exchange. The complexity of input signals and cellular collaboration generates tissue specific Th2 cell heterogeneity and specialization. In this review, we aim to discuss the advances and recent breakthroughs in our understanding of Th2 cell responses and highlight developmental and functional differences among T cells within the diversifying field of type 2 immunity. We will focus on factors provided by the tissue microenvironment and highlight factors with potential implications for the pathogenesis of allergic skin and lung diseases. Especially new insights into the role of immunometabolism, the microbiota and ionic signals enhance the complexity of Th2 cell regulation and warrant a critical evaluation. Finally, we will discuss how this ensemble of established knowledge and recent breakthroughs about Th2 immunobiology advance our understanding of the pathogenesis of allergic diseases and how this could be exploited for future immunotherapies.Keywords: Th2 cells r allergy r sodium chloride r metabolism r immunotherapy

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Th2 Cells in Health and Disease

Cited by 303 publications

References 217 publications

The Interplay between Transcription Factors and Epigenetic Modifications in Th2 Cells

The Interplay between Transcription Factors and Epigenetic Modifications in Th2 Cells

Pro‐Regenerative Glycopeptide Hydrogel Activates Type 2 Immune Response for Wound Healing via Macrophage‐T Cell Crosstalk

Shaping the diversity of Th2 cell responses in epithelial tissues and its potential for allergy treatment

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