Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes

Bogiatzi, Sofia; Fernandez, Isabel M.; Bichet, Jean Christophe; Marloie-Provost, Marie Annick; Volpe, Elisabetta; Sastre, Xavier; Soumelis, Vassili

doi:10.4049/jimmunol.178.6.3373

Cited by 245 publications

(232 citation statements)

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“…TNF-a or IL-1a), TLR ligands, and vitamin D in primary human bronchial epithelial cells and keratinocytes [16][17][18][19][20]. In such cell types, IL-13 alone did not induce TSLP production in contrast to the current results, although IL-13 was able to induce TSLP production in synergy with proinflammatory cytokines such as TNF-a [18][19][20]. The difference from the current results may be explained by the use of tissue explants in this study.…”

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

confidence: 94%

“…stromal cells) and bind to the epithelium. This issue will be clarified in our future studies.In addition, Bogiatzi et al reported that TSLP was not induced by IL-13 alone in their human skin explants [19], which was in contrast to the current results in the mouse skin explants (Supporting Information Fig. 1).…”

contrasting

confidence: 99%

“…The difference from the current results may be explained by the use of tissue explants in this study. Bogiatzi et al reported that TSLP expression was detected at the protein level when using whole skin explants, but it was not detected using a primary keratinocyte culture system [19]. Consistently, we found that IL-13, even in the presence of TNF-a, did not induce TSLP expression at the protein level in the human nasal epithelial cell line RPMI 2650 (our unpublished data).…”

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

confidence: 89%

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

confidence: 94%

contrasting

confidence: 99%

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

confidence: 89%

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

et al. 2009

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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%

“…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%

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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et al. 2010

Rook's Textbook of Dermatology

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Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes

Cited by 245 publications

References 29 publications

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

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

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

Inflammation

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