Allakhverdi Z, Comeau MR, Jessup HK 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: 13.91). 03/2007; 204(2):253-8. DOI: 10.1084/jem.20062211
Source: PubMed

ABSTRACT 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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Available from: Zoulfia Allakhverdi, Aug 25, 2015
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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 · 0.35 Impact Factor
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    • "These cytokines, produced mainly by epithelial and endothelial cells, have been reported to be critical for optimal Th2 responses and worm by guest on November 19, 2014 Downloaded from Da Silva et al. expulsion in helminth infections (Owyang et al. 2006; Allakhverdi et al. 2007b; Humphreys et al. 2008; Taylor et al. 2009). Hepworth et al. (2012) reported that innate IgEindependent regulation of tissue-derived cytokines was important for the appropriate development of an adaptive Th-2 response and the expansion of innate Th-2 cytokineproducing cells during helminthic infections. "
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    ABSTRACT: Since first described by Paul Ehrlich in 1878, mast cells have been mostly viewed as effectors of allergy. It has been only in the past two decades that mast cells have gained recognition for their involvement in other physiological and pathological processes. Mast cells have a widespread distribution and are found predominantly at the interface between the host and the external environment. Mast cell maturation, phenotype and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of an array of biologically active mediators. These features enable mast cells to act as both first responders in harmful situations as well as to respond to changes in their environment by communicating with a variety of other cells implicated in physiological and immunological responses. Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained increased prominence. Conversely, mast cell dysfunction has pointed to these cells as the main offenders in several chronic allergic/inflammatory disorders, cancer and autoimmune diseases. This review summarizes the current knowledge of mast cell function in both normal and pathological conditions with regards to their regulation, phenotype and role.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 07/2014; 62(10). DOI:10.1369/0022155414545334 · 1.22 Impact Factor
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    • "TSLP acts on many cell types including dendritic cells (DCs) [9], T cells [11] [12], mast cells [13], NKT cells [14] and eosinophils [15]. Furthermore, TSLP may act via DCs to regulate the activation, differentiation, and homeostasis of T cells [16], but it also has direct effects on T cells, promoting their survival and proliferation in response to TCR activation [17]. "
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    ABSTRACT: Background. Thymic stromal lymphopoietin (TSLP) is induced in allergic skin and lung inflammation in man and mice. Methods. Allergic lung inflammation induced by two proteases allergens HDM and papain and a classical allergen ovalbumin was evaluated in vivo in mice deficient for TSLPR. Eosinophil recruitment, Th2 and Th17 cytokine and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates and lung mononuclear cells ex vivo. Results. Here we report that mice challenged with house dust mite extract or papain in the absence of TSLPR have a drastic reduction of allergic inflammation with diminished eosinophil recruitment in BAL and lung and reduced mucus overproduction. TSLPR deficient DCs displayed diminished OVA antigen uptake and reduced capacity to activate antigen specific T cells. TSLPR deficient mice had diminished proinflammatory IL-1 β , IL-13, and IL-33 chemokines production, while IL-17A, IL-12p40 and IL-10 were increased. Together with impaired Th2 cytokines, IL-17A expressing TCR β (+) T cells were increased, while IL-22 expressing CD4(+) T cells were diminished in the lung. Conclusion. Therefore, TSLPR signaling is required for the development of both Th2 and Th22 responses and may restrain IL-17A. TSLP may mediate its effects in part by increasing allergen uptake and processing by DCs resulting in an exacerbated asthma.
    02/2013; 2013(3):971036. DOI:10.1155/2013/971036
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