Interleukin 25 promotes the initiation of proallergic type 2 responses

Angkasekwinai, Pornpimon; Park, Heon; Wang, Yui‐Hsi; Wang, Yihong; Chang, Seon Hee; Corry, David B.; Liu, Yongjun; Zhu, Zhou; Dong, Chen

doi:10.1084/jem.20061675

Cited by 504 publications

(633 citation statements)

References 27 publications

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“…12 The presence of this alteration was confirmed by matrix assisted laser desorption/ionisation time of flight (MALDI-TOF) copy number analysis (Figure 1b) and encompassed the gene encoding IL25, a cytokine known to induce Th2 immune responses. 8,9 In vitro analysis of IL25 gene expression in purified lymphocytes following T-cell activation found that this cytokine was expressed at levels 2.49-fold higher in case lymphocytes, compared with lymphocytes from control subjects (t-test P-value ¼ 0.001, Figure 1c). We therefore hypothesized that genetic amplification and overexpression of IL25 in this case may skew immunity towards Th2 responses and thereby result in insufficient Th1 immune responses.…”

Section: Resultsmentioning

confidence: 99%

“…These include the Th1-associated cytokine IL12, the Th2-associated cytokine IL5, and more recently, a newly defined member of the IL17 family, IL25, has been shown to promote Th2 responses. 8,9 Here, we describe the molecular characterization of a novel immunodeficiency disorder. This case shows profound combined immunodeficiency that manifested from an early age with recurrent Varicella infections, bronchitis, skin infections, upper respiratory tract infections and otitis media (For detailed case history, see Supplementary Information).…”

Section: Introductionmentioning

confidence: 99%

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A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

et al. 2011

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Many primary immunodeficiency disorders of differing etiologies have been well characterized, and much understanding of immunological processes has been gained by investigating the mechanisms of disease. Here, we have used a wholegenome approach, employing single-nucleotide polymorphism and gene expression microarrays, to provide insight into the molecular etiology of a novel immunodeficiency disorder. Using DNA copy number profiling, we define a hyperploid region on 14q11.2 in the immunodeficiency case associated with the interleukin (IL)-25 locus. This alteration was associated with significantly heightened expression of IL25 following T-cell activation. An associated dominant type 2 helper T cell bias in the immunodeficiency case provides a mechanistic explanation for recurrence of infections by pathogens met by Th1-driven responses. Furthermore, this highlights the capacity of IL25 to alter normal human immune responses.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

et al. 2011

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“…The expression levels of all mRNAs from untreated DC/T-cell culture represented one fold. Primer pairs used for IL-4, IL-5, IL-13, IFN-g, GATA-3, and T-bet were described previously [59].…”

Section: Real-time Pcr Analysismentioning

confidence: 99%

“…The expression levels of all mRNAs from untreated DC/T-cell culture represented one fold. Primer pairs used for IL-4, IL-5, IL-13, IFN-g, GATA-3, and T-bet were described previously [59].IgG isotype spectrum analysis C57BL/6 mice were immunized with 100 mg OVA (SigmaAldrich)1DMSO (control), me-Ant K (50 mg), or LPS (10 mg) via subcutaneous injection and boosted with the same mixtures 14 days later. Mouse sera were collected after 30 days, and OVAspecific IgG isotypes were determined by direct ELISA [60].…”

mentioning

confidence: 99%

A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

Chen

Shen

et al. 2009

Eur J Immunol

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Dendritic cells (DC) play a central role in the initiation and regulation of immune responses.Increasing evidence has indicated that manipulation of DC can serve as a therapeutic mechanism for immunomodulation. In this study we tested some unique compounds isolated from Antrodia cinnamomea, a medicinal fungus in Taiwan, on mouse bone marrowderived DC activation. A triterpenoid methyl antcinate K (me-AntK) promoted DC maturation by enhancing the expression of MHC class II, CD86, and reducing the endocytosis. TNF-a, MCP-1, and MIP-1b were secreted by DC after me-AntK treatment, indicating augmentation of innate immunity by me-AntK. Interestingly, the me-AntK-activated DC induced Ag-specific T-cell proliferation and facilitated Th2 differentiation. Examining signaling responses, we found that me-AntK treatment uniquely activated JNK and ERK in DC. Our results demonstrate that me-AntK is the first natural triterpenoid to promote the ability of DC to prime Th2 responses. This suggests that me-AntK can potentially be applied to enhance immune responses and modulate DC function in immunotherapy.Key words: DC . Immunomodulation . Th2 . Triterpenoid Supporting Information available online Introduction DC are specialized leukocytes which take up and process Ag in peripheral tissues and then transport and present Ag to activate T cells in secondary lymphoid organs [1,2]. DC are heterogeneous but all subsets have intrinsic and cooperative Ag-presenting function [3,4]. Exposure of DC to pathogen products or pro-inflammatory stimuli induces DC maturation, which dramatically enhances the ability of DC to activate Ag-specific T cells [5]. TLR are important receptors involved in detection of PAMP in DC. TLR ligation induces the activation of NF-kB and MAP kinase pathways, resulting in DC maturation, which is characterized by upregulation of MHC class II and costimulatory molecule expression as well as cytokine and chemokine production [6]. Befitting the key regulatory role of DC in 2482immune responses, DC are being developed for the treatment of cancers, allergies, and viral infections, and as adjuvants for potent new vaccines to prevent or treat cancers and infectious diseases [7,8]. Thus, DC are manipulated as pharmacological targets for discovering novel biological modifiers of immune responses [9][10][11].Natural products and their derivatives have historically been a rich source of therapeutic agents and lead molecules in drug discovery [12]. A number of biologically active natural products have been isolated from Aphyllophorales, many of which are known as polypores. Polypores are a large group of terrestrial fungi of the phylum Basidiomycota (basidiomycetes), and they are a major source of pharmacologically active substances [13]. For example, Ganoderma lucidum (Ling Zhi or Reishi), a wellknown fungus that has been used for medicinal purposes for centuries, has been studied extensively [14,15]. A precious basidiomycete Antrodia cinnamomea [syn. A. camphorata] (Ac) restrictively grows in a unique host, the endemic and en...

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“…Chronic over-expression of IL-25 in the airway epithelium resulted in asthma features such as mucus production, and airway infiltration of eosinophils and macrophages. 36 Work in this area of Th17 cytokines in the lung have actively been pursued for many pulmonary disease models.…”

Section: Transgenic Expression Of Th17 In the Lungmentioning

confidence: 99%

Transgenic modelling of cytokine polarization in the lung

et al. 2010

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SummaryThe lung is one of the commonest sites of exposure to environmental allergen or pathogen, so the expression of a variety of cytokines in the lung is dynamically regulated by inflammatory or structural cells in the lung. In the last decades, characterization of the local lung cytokine milieu in allergic or injury models has identified a collective role of certain cytokines, such as type 1 or type 2 cytokines, driving polarized inflammatory and tissue phenotypes. With the development of transgenic mouse modelling systems, the effector function of individual cytokine and the pathophysiological consequences of cytokine polarization in the lung have been effectively evaluated. Here, we present an overview of the transgenic systems currently used to assess the biological function of cytokine or other mediators in the lung. We discuss the inflammatory and tissue phenotypes detected in the lungs of transgenic mice over-expressing representative T helper type 1 (interferon-c, interleukin-12), T helper type 2 (interleukins -4, -5, -9, -10 and -13), and T helper type 17 cytokines. The effects of genetic modification of cytokine receptors or transcriptional factors such as GATA-3 and T-bet in pulmonary inflammation and remodelling tissue responses are also discussed because these transcription factors are regarded as essential regulators of cytokine polarization. Finally, we discuss the limitations and future application of transgenic approaches in the studies of human lung diseases characterized by cytokine polarization.

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Interleukin 25 promotes the initiation of proallergic type 2 responses

Cited by 504 publications

References 27 publications

A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation

Transgenic modelling of cytokine polarization in the lung

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