The influence of TSLP on the allergic response

Inflammation Research, Amgen Inc., Seattle, Washington, USA.
Mucosal Immunology (Impact Factor: 7.37). 12/2009; 3(2):138-47. DOI: 10.1038/mi.2009.134
Source: PubMed


Exposure to allergens first occurs at body surfaces in direct contact with the environment such as the skin, airways, and gastrointestinal tract, and compelling evidence suggests that allergic inflammatory responses are profoundly influenced by the products of epithelial cells located at these sites. One such product is thymic stromal lymphopoietin (TSLP), which is capable of affecting multiple cell lineages involved in allergic reactions. In this review we discuss recent work that has provided insight into the role TSLP plays in both aberrant and protective allergic inflammatory responses, as well as regulation, associations with disease, sources, and functions of this important cytokine.

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Available from: Michael R Comeau, Aug 14, 2014
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    • "‘Food allergy’ can be described as an exaggerated immune response to certain ingredients present in food and chiefly characterised by the production of immunoglobulin E (IgE) antibodies [1], [2]. These IgE antibodies have been shown to have high affinity to receptors on immune cells such as mast cells and basophils [3] and interactions with these cells can lead to the release of potent mediators and the development of allergy symptoms [4], [5]. The symptoms of allergy can range from mild reactions (e.g. "
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    ABSTRACT: Peanut allergy is the leading cause of deaths due to food-induced anaphylaxis but despite continued research, there are currently no specific treatments available. Challenge testing is limited in patients due to the high risk of adverse reactions, emphasising the need for an appropriate animal model. In the present study we examine the induction of allergic responses in a sheep model for peanut allergy. Sheep were sensitised with peanut (PN) extract and in separate injections with ovalbumin (OVA) or house dust mite (HDM) extract. Serum PN-specific IgE responses were detected in 40-50% of immunised sheep, while only 10% (1 of 10 sheep) showed detectable OVA-specific IgE. All PN-allergic sheep tested showed an Ara h 1-specific IgE response, while four out of five allergic sheep showed an Ara h 2-specific IgE response. Animals with high serum IgE levels to HDM were also PN IgE-positive. Of the PN-sensitised animals with high PN-specific IgE, 80% also showed an immediate hypersensitivity reaction following an intradermal PN injection. This new large animal model of peanut allergy may provide a useful tool for future investigations of allergen-associated immune mechanisms and specific immunotherapy.
    PLoS ONE 12/2012; 7(12):e51386. DOI:10.1371/journal.pone.0051386 · 3.23 Impact Factor
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    • "One possible candidate that has been linked to the initiation of inflammatory responses in AD and other allergic diseases is thymic stromal lymphopoietin (TSLP), a member of the hematopoietic cytokine family. It is expressed at a low level primarily by epithelial cells, including keratinocytes, upregulated in acute and chronic AD lesions and responsible for activating cutaneous DCs, endowing them with the capacity to polarize CD4+ T cells toward a Th2 cell allergic response [9]–[12]. TSLP signals through a heterodimeric receptor formed by TSLP receptor (TSLPR) as well as IL-7 receptor alpha (IL7Rα) [9]. "
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    ABSTRACT: Background Ctip2 is crucial for epidermal homeostasis and protective barrier formation in developing mouse embryos. Selective ablation of Ctip2 in epidermis leads to increased transepidermal water loss (TEWL), impaired epidermal proliferation, terminal differentiation, as well as altered lipid composition during development. However, little is known about the role of Ctip2 in skin homeostasis in adult mice. Methodology/Principal Findings To study the role of Ctip2 in adult skin homeostasis, we utilized Ctip2ep−/− mouse model in which Ctip2 is selectively deleted in epidermal keratinocytes. Measurement of TEWL, followed by histological, immunohistochemical, and RT-qPCR analyses revealed an important role of Ctip2 in barrier maintenance and in regulating adult skin homeostasis. We demonstrated that keratinocytic ablation of Ctip2 leads to atopic dermatitis (AD)-like skin inflammation, characterized by alopecia, pruritus and scaling, as well as extensive infiltration of immune cells including T lymphocytes, mast cells, and eosinophils. We observed increased expression of T-helper 2 (Th2)-type cytokines and chemokines in the mutant skin, as well as systemic immune responses that share similarity with human AD patients. Furthermore, we discovered that thymic stromal lymphopoietin (TSLP) expression was significantly upregulated in the mutant epidermis as early as postnatal day 1 and ChIP assay revealed that TSLP is likely a direct transcriptional target of Ctip2 in epidermal keratinocytes. Conclusions/Significance Our data demonstrated a cell-autonomous role of Ctip2 in barrier maintenance and epidermal homeostasis in adult mice skin. We discovered a crucial non-cell autonomous role of keratinocytic Ctip2 in suppressing skin inflammatory responses by regulating the expression of Th2-type cytokines. It is likely that the epidermal hyperproliferation in the Ctip2-lacking epidermis may be secondary to the compensatory response of the adult epidermis that is defective in barrier functions. Our results establish an initiating role of epidermal TSLP in AD pathogenesis via a novel repressive regulatory mechanism enforced by Ctip2.
    PLoS ONE 12/2012; 7(12-12):e51262. DOI:10.1371/journal.pone.0051262 · 3.23 Impact Factor
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    • "Several cellular targets of TSLP have been identified, including dendritic cells, lymphocytes, and granulocytes. TSLP-stimulated dendritic cells are able to activate CD4+ T cells in an antigen-specific manner, resulting in T cells with the Th2 phenotype that produce proallergic cytokines (IL-4, IL-5, IL-13, and TNF-α), while down-regulating IL-10 and IFN-γ [2]. Studies of TSLP in humans have indicated its potential role in the Th2 inflammatory response. "
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    ABSTRACT: Background Graves disease (GD) is an organ-specific autoimmune disease characterized by hyperthyroidism, diffuse goiter, autoantibodies against thyroid-specific antigens, and dermopathy. Studies of GD have demonstrated the importance of the Th2 and Th17 immune responses in mediating disease progression. In the present study, we investigated the role of a Th2 cytokine, thymic stromal lymphopoietin (TSLP), in GD and Th17 differentiation. Methods In this study, we genotyped 470 patients with GD at 3 single nucleotide polymorphisms (SNPs) in TSLP. In addition, the serum concentrations of TSLP were determined in 432 patients and 272 controls. Ten patients and controls each were further screened using in vitro Th17 differentiation assays. The SNPs were genotyped using ABI TaqMan® SNP genotyping assays. For the Th17 differentiation assays, peripheral blood mononuclear cells (PBMCs) isolated from the patients and controls were placed into Th17 differentiation media, and interleukin 17 expression levels were determined. Results Haplotype analysis indicated that patients with the Ht3 (TCC) haplotype have a 3.28-fold higher risk of developing GD (p = 0.007), whereas those with the Ht5 (TCG) haplotype had a 0.03-fold, reduced risk of developing GD (p = 1 × 10−14). SNP rs3806933 (p = 0.007) was associated with female Graves ophthalmopathy (GO). TSLP expression levels were higher in GD patients than in control subjects, and TLSP was also shown to promote the differentiation of Th17 cells in GD patients. Conclusions These results suggest that polymorphisms in TSLP may be used as genetic markers for the diagnosis and prognosis of GD. Furthermore, TLSP may be a target for treating GD.
    BMC Medical Genetics 11/2012; 13(1):116. DOI:10.1186/1471-2350-13-116 · 2.08 Impact Factor
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