A conserved enhancer regulates Il9 expression in multiple lineages

Koh, Byunghee; Qayum, Amina Abdul; Srivastava, Rajneesh; Fu, Yukui; Ulrich, Bernd; Janga, Sarath Chandra; Kaplan, Mark H.

doi:10.1038/s41467-018-07202-0

Cited by 28 publications

(49 citation statements)

References 68 publications

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“…Commitment to the TH9 lineage is the result of a number of TFs acting in concert. Recent ChIP‐sequencing studies identified binding of IRF4, BATF, STAT5, STAT6, PU.1, GATA3, and FOXO1 at five different regulatory regions of IL9 including the promoter (Koh et al, ). IL4, required in vitro in addition to TGFβ, promotes TH9 differentiation, in part by pSTAT6 inhibiting TGFβ‐induced FOXP3 and T‐bet expression and therefore inhibiting Treg and TH1 polarization (Dardalhon et al, ; Kaplan et al, ).…”

Section: Discussionmentioning

confidence: 99%

Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation

Li²,

Ye³

et al. 2019

Aging Cell

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With reduced thymic activity, the population of naïve T cells in humans is maintained by homeostatic proliferation throughout adult life. In young adults, naïve CD4 T cells have enormous proliferative potential and plasticity to differentiate into different lineages. Here, we explored whether naïve CD4 T‐cell aging is associated with a partial loss of this unbiased multipotency. We find that naïve CD4 T cells from older individuals have developed a propensity to develop into TH9 cells. Two major mechanisms contribute to this predisposition. First, responsiveness to transforming growth factor β (TGFβ) stimulation is enhanced with age due to an upregulation of the TGFβR3 receptor that results in increased expression of the transcription factor PU.1. Secondly, aged naïve CD4 T cells display altered transcription factor profiles in response to T‐cell receptor stimulation, including enhanced expression of BATF and IRF4 and reduced expression of ID3 and BCL6. These transcription factors are involved in TH9 differentiation as well as IL9 transcription suggesting that the aging‐associated changes in the transcription factor profile favor TH9 commitment.

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Section: Discussionmentioning

confidence: 99%

Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation

Li²,

Ye³

et al. 2019

Aging Cell

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“…BATF and IRF‐4 cooperatively contribute to Th9 cell development . CNS‐25 acts as an enhancer upstream of the il9 gene binding most IL‐9 promoting transcription factors, as could be shown in mice . TL1A, which represents a member of the TNF superfamily, promotes Th9 differentiation, and function through induction of transcriptional BATF3 expression in mice and humans .…”

Section: Il‐9 Producing Th2‐like Cellsmentioning

confidence: 93%

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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“…(Bi et al, 2017;Buttrick et al, 2018;Campos Carrascosa et al, 2017;Kaplan et al, 2015). Like other cytokine genes, the Il9 locus has a complex enhancer structure (Koh et al, 2018;Schwartz et al, 2019).…”

Section: Regulation Of Expression Of G C Family Cytokinesmentioning

confidence: 99%

The γc Family of Cytokines: Basic Biology to Therapeutic Ramifications

2019

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The common cytokine receptor g chain, g c , is a component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. Mutation of the gene encoding g c results in X-linked severe combined immunodeficiency in humans, and g c family cytokines collectively regulate development, proliferation, survival, and differentiation of immune cells. Here, we review the basic biology of these cytokines, highlighting mechanisms of signaling and gene regulation that have provided insights for immunodeficiency, autoimmunity, allergic diseases, and cancer. Moreover, we discuss how studies of this family stimulated the development of JAK3 inhibitors and present an overview of current strategies targeting these pathways in the clinic, including novel antibodies, antagonists, and partial agonists. The diverse roles of these cytokines on a range of immune cells have important therapeutic implications.

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A conserved enhancer regulates Il9 expression in multiple lineages

Cited by 28 publications

References 68 publications

Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation

Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation

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

The γc Family of Cytokines: Basic Biology to Therapeutic Ramifications

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