Allakhverdi Z, Comeau MR, Jessup HK, Yoon B-R, Brewer A, Chartier S et al.Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J Exp Med 204:253-258

Laboratory on Allergy, CHUM Research Center, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
Journal of Experimental Medicine (Impact Factor: 12.52). 03/2007; 204(2):253-8. DOI: 10.1084/jem.20062211
Source: PubMed


Compelling evidence suggests that the epithelial cell-derived cytokine thymic stromal lymphopoietin (TSLP) may initiate asthma or atopic dermatitis through a dendritic cell-mediated T helper (Th)2 response. Here, we describe how TSLP might initiate and aggravate allergic inflammation in the absence of T lymphocytes and immunoglobulin E antibodies via the innate immune system. We show that TSLP, synergistically with interleukin 1 and tumor necrosis factor, stimulates the production of high levels of Th2 cytokines by human mast cells (MCs). We next report that TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines. Direct epithelial cell-mediated, TSLP-dependent activation of MCs may play a central role in "intrinsic" forms of atopic diseases and explain the aggravating role of infection and scratching in these diseases.

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    • "De plus, certains stimuli favorisent la production de cytokines/chimiokines en absence d'une réponse de dégranulation, comme c'est par exemple le cas pour le TLR2 et le TLR4 [29], l'IL-1 [30], l'IL-33 [31] ou encore le TSLP [32]. De manière intéressante, alors que la stimulation de ces récepteurs favorise Pour citer cet article : Blank U, Vitte J. Les médiateurs du mastocyte. "
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    ABSTRACT: Mast cells are resident cells, mostly found in interface tissues. They are endowed with a rich granular contents that led their discoverer, Paul Ehrlich, to hypothesize on their nutritional role. Although the first description of mast cells dated back to 1878, their effector role in immediate type hypersensitivity was not uncovered until 1950, while their more general role in immune functions were largely unknown until 2000. In the present review, we will summarize the current understanding of exocytosed mast cell mediators, together with the mechanisms of membrane fusion that govern the degranulation/exocytosis process.
    Revue Française d'Allergologie 11/2014; 55(1). DOI:10.1016/j.reval.2014.10.002 · 0.25 Impact Factor
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    • "TSLP derived from ECs is a key allergic inflammation master switch [20], [21], [30], suggesting that it is the most important target interfering with the initial phase of allergic diseases [31]–[33]. Most studies have shown that epithelial cells are the main source of TSLP production [34]–[36]. These results directly confirm the link between TSLP and allergic inflammation. "
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    ABSTRACT: Yu-ping-feng-san (YPFS) is a Chinese medical formula that is used clinically for allergic diseases and characterized by reducing allergy relapse. Our previous studies demonstrated that YPFS efficiently inhibited T helper 2 cytokines in allergic inflammation. The underlying mechanisms of action of YPFS and its effective components remain unclear. In this study, it was shown that YPFS significantly inhibited production of thymic stromal lymphopoietin (TSLP), an epithelial cell-derived initiative factor in allergic inflammation, in vitro and in vivo. A method of human bronchial epithelial cell (16HBE) binding combined with HPLC-MS (named 16HBE-HPLC-MS) was established to explore potential active components of YPFS. The following five components bound to 16HBE cells: calycosin-7-glucoside, ononin, claycosin, sec-o-glucosylhamaudol and formononetin. Serum from YPFS-treated mice was analyzed and three major components were detected claycosin, formononetin and cimifugin. Among these, claycosin and formononetin were detected by 16HBE-HPLC-MS and in the serum of YPFS-treated mice. Claycosin and formononetin decreased the level of TSLP markedly at the initial stage of allergic inflammation in vivo. Nuclear factor (NF)-κB, a key transcription factor in TSLP production, was also inhibited by claycosin and formononetin, either in terms of transcriptional activation or its nuclear translocation in vitro. Allergic inflammation was reduced by claycosin and formononetin when they are administered only at the initial stage in a murine model of atopic contact dermatitis. Thus, epithelial cell binding combined with HPLC-MS is a valid method for screening active components from complex mixtures of Chinese medicine. It was demonstrated that the compounds screened from YPFS significantly attenuated allergic inflammation probably by reducing TSLP production via regulating NF-κB activation.
    PLoS ONE 09/2014; 9(9):e107279. DOI:10.1371/journal.pone.0107279 · 3.23 Impact Factor
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    • "Extensive investigations have revealed a salient abnormality of AD skin lesions in which an interleukin (IL)-7-like cytokine, thymic stromal lymphopoietin (TSLP), produced by keratinocytes provokes a hyperreactive immune state [4], [5], [6]. In AD lesions, TSLP activates myeloid dendritic cells and then promotes the differentiation of naïve CD4+ T cells into T helper type 2 (Th2) cells secreting IL-4, IL-5 and IL-13, in a manner similar to that in allergic asthma. "
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    ABSTRACT: In the skin lesions of atopic dermatitis (AD), keratinocytes release large quantities of thymic stromal lymphopoietin (TSLP), causing unfavorable inflammation along with skin damage. Nevertheless, how TSLP influences keratinocytes themselves is still unknown. In this study, we showed that ΔNp63, a p53-homologue, predominantly expressed in keratinocytes regulated the receptor complex of TSLP, which determines susceptibility to self-derived TSLP. Expression of TSLP receptors in skin tissues and keratinocytes was assessed by immunohistochemistry and quantitative RT-PCR, and in vitro studies were also performed to examine the functional relevance of ΔNp63 in the expression of TSLP receptors and the constituting autocrine and/or paracrine pathway of TSLP under the condition of stimuli to innate receptors sensing cell damage. The results showed that normal keratinocytes in the upper epidermis preferentially expressed TSLP receptors and conversely lacked ΔNp63, which has an inhibitory effect on the expression of TSLP receptors. Interestingly, the epidermis of AD lesions was found to abundantly contain keratinocytes with low or undetectable levels of ΔNp63 (ΔNp63lo/-). Moreover, in the absence of ΔNp63, keratinocytes readily presented TSLP and other cytokines by stimuli through Toll-like receptor 3 (TLR3). Together with the evidence that extrinsic TSLP itself augments TSLP production by keratinocytes without ΔNp63, the results indicate that ΔNp63lo/- keratinocytes generate TSLP through a putative autocrine and/or paracrine pathway upon TLR3 stimulation within AD lesions, since moieties of damaged cells and pathogens stimulate TLR3.
    PLoS ONE 08/2014; 9(8):e105498. DOI:10.1371/journal.pone.0105498 · 3.23 Impact Factor
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