TH9 cells are required for tissue mast cell accumulation during allergic inflammation

Sehra, Sarita; Yao, Weiguo; Nguyen, Evelyn T.; Glosson-Byers, Nicole L.; Akhtar, Nahid; Zhou, Baohua; Kaplan, Mark H.

doi:10.1016/j.jaci.2015.01.021

Cited by 153 publications

(158 citation statements)

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“…Importantly, while we and others have shown that the HDM model of airway inflammation is dependent on IL-17 (22, 43), the OVA-alum model is largely IL-17 independent (44), so that the effects of ETV5-deficiency on IL-17 should not impact the total cellular inflammation in our studies. Both ETV5 and PU.1 contribute to the ability of Th9 cells to promote accumulation and gene expression of mast cells in lung tissue, again consistent with our previous results on the role of Th9 cells in mast cell accumulation in multiple models of allergic airway disease (45). We did observe that IL-13-producing T cells in the lung were also decreased in mice with T cells lacking both ETV5 and PU.1, though the proportion of these cells was not different, suggesting the decrease in number was linked to decreased overall inflammation.…”

Section: Discussionsupporting

confidence: 91%

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The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To Promote Th9 Cell Development

Koh

Hufford

Pham

et al. 2016

The Journal of Immunology

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The IL-9-secreting Th9 subset of CD4 T helper cells develop in response to an environment containing IL-4 and TGFβ, promoting allergic disease, autoimmunity, and resistance to pathogens. We previously identified a requirement for the ETS family transcription factor PU.1 in Th9 development. In this report we demonstrate that the ETS transcription factor ETV5 promotes IL-9 production in Th9 cells by binding and recruiting histone acetyltransferases to the Il9 locus at sites distinct from PU.1. In cells that are deficient in both PU.1 and ETV5 there is lower IL-9 production than in cells lacking either factor alone. In vivo loss of PU.1 and ETV5 in T cells results in distinct affects on allergic inflammation in the lung, suggesting that these factors function in parallel. Together, these data define a role for ETV5 in Th9 development and extend the paradigm of related transcription factors having complementary functions during differentiation.

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Section: Discussionsupporting

confidence: 91%

“…Among these, the CD4-Cre should only affect expression in NKT cells. We previously suggested that PU.1 was not required for IL-9 production by NKT cells (45), but it is not clear if ETV5 might play a role within these cells. The role of NKT cells in asthma models is still debated, and what controls IL-9 within these cells is not yet clear.…”

Section: Discussionmentioning

confidence: 99%

The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To Promote Th9 Cell Development

Koh

Hufford

Pham

et al. 2016

The Journal of Immunology

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“…IL-25 secretion by epithelial tuft cells also may aid the expansion of type 2 innate lymphoid cell (ILC2) populations 174 , which together with T H 2 cells secrete cytokines that promote the T H 2 cell-mediated immune response 175 , which includes tissue eosinophil accumulation and IgE class-switching by B cells 20 . T H 9 cells also contribute to the allergic immune response by increasing tissue mast cell accumulation 176 , and IL-4-mediated signalling may convert regulatory T cells into T H 2 cells 62 . The roles of follicular T cells, tissue-resident T cells, CD8 + T cells and γδ T cells remain to be determined.…”

Section: Figurementioning

confidence: 99%

Food allergy: immune mechanisms, diagnosis and immunotherapy

2016

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Food allergy is a pathological, potentially deadly, immune reaction triggered by normally innocuous food protein antigens. The prevalence of food allergies is rising and the standard of care is not optimal, consisting of food-allergen avoidance and treatment of allergen-induced systemic reactions with adrenaline. Thus, accurate diagnosis, prevention and treatment are pressing needs, research into which has been catalysed by technological advances that are enabling a mechanistic understanding of food allergy at the cellular and molecular levels. We discuss the diagnosis and treatment of IgE-mediated food allergy in the context of the immune mechanisms associated with healthy tolerance to common foods, the inflammatory response underlying most food allergies, and immunotherapy-induced desensitization. We highlight promising research advances, therapeutic innovations and the challenges that remain.

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“…For example, in an OVA model, enhanced mast cell accumulation followed adoptive transfer of T H 9 cells but not T H 2 cells, and this effect was dependent on T cell–derived IL-9. 136 Analysis of T H 9 cells in relation to asthma phenotypes in human subjects could shed more light on their role.…”

Section: Heterogeneity Of T Cells and Influence Of The Tissue Microenmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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TH9 cells are required for tissue mast cell accumulation during allergic inflammation

Cited by 153 publications

References 50 publications

The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To Promote Th9 Cell Development

The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To Promote Th9 Cell Development

Food allergy: immune mechanisms, diagnosis and immunotherapy

Pathogenic CD4 + T cells in patients with asthma

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