Th2 and Th9 responses in patients with chronic mucocutaneous candidiasis and hyper‐IgE syndrome

Becker, Katharina L.; Rösler, Berenice; Wang, X.; Lachmandas, Ekta; Kamsteeg, Marijke; Jacobs, Cor; Joosten, Leo A. B.; Netea, Mihai G.; Veerdonk, Frank L. van de

doi:10.1111/cea.12787

Cited by 26 publications

(17 citation statements)

References 38 publications

(38 reference statements)

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“…TAK1 inhibition decreases and Id3 siRNA increases IL-9, similar to the effects of these approaches in the murine system [43]. T cells from patients with mutations in STAT1 (Chronic Mucocutaneous Candidiasis) and STAT3 (Hyper-IgE Syndrome) have diminished IL-9 production, compared to healthy controls, suggesting somewhat distinct effects of these pathways between murine and patient systems [82]. …”

Section: The Human Th9 Transcription Factor Networkmentioning

confidence: 93%

The transcription factor network in Th9 cells

Kaplan

2016

Semin Immunopathol

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The development of T helper cell subsets requires activated T cells that respond to a polarizing cytokine environment resulting in the activation and expression of transcription factors. The subset-specific transcription factors bind and induce the production of specific effector cytokines. Th9 cells express IL-9 and develop in the presence of TGFβ, IL-4, and IL-2. Each of these cytokines activates signaling pathways that are required for Th9 differentiation and IL-9 production. In this review I summarize what is currently understood about the signaling pathways and transcription factors that promote the Th9 genetic program, providing some perspective for the integration of the signals in regulating the Il9 gene and dictating the expression of other Th9-associated genes. I highlight how experiments in mouse cells have established a transcriptional network that is conserved in human T cells, and set the stage towards defining the next important questions for a more detailed understanding of Th9 cell development and function.

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Section: The Human Th9 Transcription Factor Networkmentioning

confidence: 93%

The transcription factor network in Th9 cells

Kaplan

2016

Semin Immunopathol

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“…In healthy volunteers, the fungal pathogen C. albicans induced IL-9 production, mostly by IL-9 + IL-17 + -co-expressing CD4 + T cells than IL-9 single positive cells. However in patients with hyper IgE syndrome (HIES) caused by STAT3 mutation, this IL-9 response was significantly lower in the presence of IL-4, which could be due to the deficiency of Th17 cell subset in these patients [ 91 ]. The Th9 subset plays a role in the allergic response to A. fumigatus in cystic fibrosis, and blockade of the Th9 response in this setting could represent a novel therapeutic strategy to reduce infection associated inflammation [ 92 ].…”

Section: Th2 Response Drives Allergic Hypersensitivity Reactions Tmentioning

confidence: 99%

The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus fumigatus

Dewi

Veerdonk

Gresnigt

2017

JoF

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The ubiquitous opportunistic fungal pathogen Aspergillus fumigatus rarely causes infections in immunocompetent individuals. A healthy functional innate immune system plays a crucial role in preventing Aspergillus-infection. This pivotal role for the innate immune system makes it a main research focus in studying the pathogenesis of aspergillosis. Although sometimes overshadowed by the innate immune response, the adaptive immune response, and in particular T-helper responses, also represents a key player in host defense against Aspergillus. Virtually all T-helper subsets have been described to play a role during aspergillosis, with the Th1 response being crucial for fungal clearance. However; morbidity and mortality of aspergillosis can also be partly attributed to detrimental immune responses resulting from adaptive immune activation. Th2 responses benefit fungal persistence; and are the foundation of allergic forms of aspergillosis. The Th17 response has two sides; although crucial for granulocyte recruitment, it can be involved in detrimental immunopathology. Regulatory T-cells, the endogenous regulators of inflammatory responses, play a key role in controlling detrimental inflammatory responses during aspergillosis. The current knowledge of the adaptive immune response against A. fumigatus is summarized in this review. A better understanding on how T-helper responses facilitate clearance of Aspergillus-infection and control inflammation can be the fundamental basis for understanding the pathogenesis of aspergillosis and for the development of novel host-directed therapies.

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“…Similar to other T helper cell subsets, primary immunodeficiencies can be used to delineate the signaling pathways and molecular requirements for the generation and function of human Th9 cells. Indeed, two groups have assessed IL‐9‐expressing cells in patients with STAT3 LOF and STAT1 GOF mutations . Memory CD4 + T cells from both STAT3 LOF and STAT1 GOF patients exhibited significantly decreased production of IL‐9 in vitro , indicating both of these transcription factors are involved in regulating human Th9 cell generation.…”

Section: Utilizing Primary Immunodeficiencies To Investigate Human Thmentioning

confidence: 99%

What can primary immunodeficiencies teach us about Th9 cell differentiation and function?

2018

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Interleukin-9 (IL-9) producing CD4 + Th9 cells are a unique subset of effector cells involved in both health and disease. Th9 cells have been associated with protective immunity during parasitic infections with helminths, protozoans and extracellular pathogens, but implicated in disease states such as allergic asthma, atopic dermatitis, food allergy and autoimmune conditions including multiple sclerosis and ulcerative colitis. Here, we review the cytokine signaling pathways and downstream transcription factors required for IL-9 expression and how human primary immunodeficiencies caused by monogenic mutations can help elucidate the complex requirements for human Th9 cell differentiation. Primary immunodeficiencies are a platform for investigating IL-9 expression in primary human lymphocytes and by inference whether Th9 cells are implicated in the clinical phenotype characteristic of these patients.

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Th2 and Th9 responses in patients with chronic mucocutaneous candidiasis and hyper‐IgE syndrome

Cited by 26 publications

References 38 publications

The transcription factor network in Th9 cells

The transcription factor network in Th9 cells

The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus fumigatus

What can primary immunodeficiencies teach us about Th9 cell differentiation and function?

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