Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells

Allakhverdi, Zoulfia; Comeau, Michael R.; Jessup, Heidi K.; Yoon, Bo-Rin Park; Brewer, Avery W.; Chartier, Suzanne; Paquette, Nicole C.; Ziegler, Steven F.; Sarfati, Marika; Delespesse, Guy

doi:10.1084/jem.20062211

Cited by 685 publications

(684 citation statements)

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“…This is consistent with recent in vitro studies, which suggest that TSLP expression in epithelial cells requires proinflammatory cytokines such as TNF-a [11][12][13]. Therefore, it is possible that mast cell-derived inflammatory cytokines including TNF-a generated at the site of allergic rhinitis may play an important role for the induction of TSLP expression in the nasal epithelium.…”

Section: Tslp Is Critical For the Development Of Allergic Rhinitissupporting

confidence: 91%

“…Conversely, TSLP has been shown to stimulate the production of high levels of Th2 cytokines by human mast cells synergistically with IL-1 and TNF-a [12]. Therefore, it is possible that there is an important interaction between epithelial cells and mast cells via TSLP and proinflammatory cytokines for the development of allergic rhinitis.…”

Section: Tslp Is Critical For the Development Of Allergic Rhinitismentioning

confidence: 99%

“…Previous studies suggest that TSLP expression in mouse keratinocytes is regulated by vitamin D and retinoic acid signaling [10]. Most recently, TNF-a, IL-1b, and ligands for Toll-like receptors such as LPS were shown to up-regulate TSLP expression via NF-jB pathway in cultured human bronchial epithelial cells and keratinocytes [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Mast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitis

et al. 2008

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Epithelial cell-derived thymic stromal lymphopoietin (TSLP) is a master switch for asthma or atopic dermatitis by inducing a dendritic cell-mediated Th2-type allergic inflammation. Allergic rhinitis is also pathologically characterized by Th2-type allergic inflammation. This study demonstrates that mast cells regulate the epithelial TSLP expression in allergic rhinitis. TSLP expression was found to be up-regulated predominantly in the nasal epithelium in the ovalbumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis, which was abolished in mast cell-deficient WBB6F1-W/W v in comparison with control WBB6F1-+/+ mice. Similarly, the epithelial TSLP expression was reduced in Fc receptor c chain (FccR)-deficient mice, where the high-affinity IgE receptor (FceRI) is not expressed on mast cells, in comparison with control C57BL/6 mice. Furthermore, the administration of neutralizing TSLP antibody during the challenge phase of OVA inhibited the development of allergic rhinitis. These results suggest that the direct stimulation of epithelial cells by antigens alone may not be sufficient to induce TSLP expression in the nasal epithelium, and that mast cell regulation of epithelial TSLP expression, possibly via FceRI, plays an important role in the development of allergic rhinitis. Key words: Allergic rhinitis Á Epithelial cells Á Mast cells Á TSLP IntroductionThymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which binds to a TSLP receptor (TSLPR) consisting of the IL-7 receptor a-chain (IL-7Ra) and a common c receptor-like chain (TSLPR-c) [1,2]. TSLP was originally identified as a factor derived from a thymic stromal cell line that could support the growth of a mouse B cell line [3]. However, recently, TSLP, derived from epithelial cells, has been shown to be capable of activating CD11c + myeloid DC to up-regulate costimulatory molecules, leading to the differentiation of CD4 + T cells into Th2 cells. Therefore, it plays a key role in the development of allergic diseases such as asthma or atopic dermatitis [1,2,4]. For instance, transgenic mice expressing TSLP in keratinocytes or in lung epithelial cells have been shown to develop atopic dermatitis-or asthma-like inflammation in the skin or the lung, respectively, while TSLPR null mice failed to develop an inflammatory lung response to inhaled antigen [5][6][7]. In humans, TSLP has been shown to be expressed by keratinocytes in atopic dermatitis and by bronchial epithelial cells in asthmatic airways [8,9].In contrast to the pro-allergic action of TSLP, regulation of TSLP expression in epithelial cells has not been fully elucidated. Previous studies suggest that TSLP expression in mouse keratinocytes is regulated by vitamin D and retinoic acid signaling [10] [17]. In addition, mast cells up-regulate the production of a variety of cytokines/chemokines in epithelial cells and fibroblasts, and induce the recruitment of basophils, T cells, and eosinophils into sites of allergic inflammation as well as their own intraepithelial accumulation....

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Section: Tslp Is Critical For the Development Of Allergic Rhinitissupporting

confidence: 91%

Section: Tslp Is Critical For the Development Of Allergic Rhinitismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitis

et al. 2008

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“…1 and Supporting Information Fig. 1), which was consistent with the findings observed in human skin explants [21]. Endogenous stimulators of TSLP production might be released upon the cellular damage associated with the tissue isolation and contribute to the basal TSLP production.…”

Section: Il-13 Induces Tslp Expression In Normal Trachea Lung and Ssupporting

confidence: 88%

Thymic stromal lymphopoietin is a critical mediator of IL‐13‐driven allergic inflammation

et al. 2009

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Both thymic stromal lymphopoietin (TSLP) and IL-13 are essential cytokines for the development of allergic inflammation. However, a causal link between TSLP and IL- 13 has not yet been fully elucidated. This study aimed to investigate whether IL-13 induces TSLP expression and whether the induction contributes to the development of allergic inflammation. We found that IL-13 induced TSLP expression in mouse nasal tissue specimens in a Stat6-dependent manner. In addition, intranasal challenge of mice with IL-13 induced TSLP expression in the nasal epithelium. Importantly, intranasal IL-13 challenge induced eosinophilia and goblet cell hyperplasia in the nasal mucosa in mice, which was inhibited by the blockade of TSLP activity with anti-TSLP Ab. These findings suggest that TSLP is an important mediator of IL-13-driven allergic inflammation in the nasal mucosa. Taken together with the recent findings that IL-13 is a critical downstream element for TSLP-driven allergic inflammation, TSLP may function both upstream and downstream of IL-13, thus providing an additional rationale as to why TSLP plays such a central role in the development of allergic inflammation.Key words: Allergic inflammation . Epithelial cells . IL-13 . Thymic stromal lymphopoietin Supporting Information available online IntroductionThymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which binds to a TSLP receptor (TSLPR) consisting of the IL-7 receptor a-chain and a common g receptor-like chain [1,2]. TSLP was originally identified as a factor derived from a thymic stromal cell line that could support the growth of a mouse B-cell line [3].However, recent evidence has demonstrated TSLP, derived from epithelial cells, to be a critical factor for allergic inflammation [1,2,4]. For instance, transgenic mice expressing TSLP in keratinocytes or in lung epithelial cells develop atopic dermatitisor asthma-like inflammation in the skin or the lung, respectively, while TSLPR-deficient mice fail to develop an inflammatory lung response to inhaled antigen [5][6][7].IL-13, a Th2-type cytokine, is a central mediator for allergic inflammation [8,9]. The blockade of IL-13 markedly inhibits allergen-induced airway hyperresponsiveness, mucus production, and eosinophilia whereas IL-13 delivery to the airway causes SHORT COMMUNICATION 3078these effects in mice [8][9][10][11]. Therefore, IL-13 as well as TSLP is necessary and sufficient for the development of allergic inflammation. However, the relationship between TSLP and IL-13 in allergic inflammation has not yet been fully elucidated.This study thus investigated the causal link between IL-13 and TSLP in allergic inflammation. For this purpose, we examined the effects of IL-13 on TSLP expression both in vitro and in vivo using mouse nasal tissue explants and a mouse model of allergic inflammation in the nasal mucosa, respectively. The current results suggest that TSLP is induced by IL-13 and is critical for the development of IL-13-driven allergic inflammation. Because recent studies suggest that TSLP-dri...

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“…TSLP can stimulate mast cells and dendritic cells to initiate the innate allergic immune responses. 95 In the latter phases, TSLP activated DCs mediate the T cell dependent adaptive phase of the allergic immune response.…”

Section: Mast Cellsmentioning

confidence: 99%

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

Sehra

Tuana

Holbreich

et al. 2008

An. Bras. Dermatol.

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Atopic dermatitis is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10-20 % of infants and 1-3% of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. Probably half of the children with atopic dermatitis develop some other form of atopic disease later in life. The pathogenesis involves a complex interplay of factors including genetic predisposition due to altered immune or skin barrier function, interactions with the environment such as food and allergen exposures, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of atopic dermatitis and how insights provide new therapeutic potential for its treatment. Keywords: Asthma; Atopic Dermatitis, Eczema; Eosinophils; Genetics; Immunoglobulin E; Keratinocytes; Rhinitis, T-Lymphocytes Resumo: A dermatite atópica é uma doença cutânea inflamatória crônica cuja prevalência tem aumentado de forma constante, afetando 10-20% dos lactentes e 1-3% dos adultos em todo o mundo. Ela é freqüentemente a primeira manifestação clínica de doença atópica, precedendo a asma e a rinite alérgica. Provavelmente metade das crianças com dermatite atópica desenvolvem alguma

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Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells

Cited by 685 publications

References 28 publications

Mast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitis

Mast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitis

Thymic stromal lymphopoietin is a critical mediator of IL‐13‐driven allergic inflammation

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

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