Long TSLP transcript expression and release of TSLP induced by TLR ligands and cytokines in human keratinocytes

Xie, Yang; Takai, Toshiro; Xue, Cong; Okumura, Ko; Ogawa, Hideoki

doi:10.1016/j.jdermsci.2012.03.007

Cited by 81 publications

(82 citation statements)

References 30 publications

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“…These results suggest the possibility that TNF-a induces TSLP expression in an autocrine and/or paracrine manner in keratinocytes of AD lesions. In vitro, real time-quantitative PCR (qPCR) and ELISA analyses showed that TNF-a increased both TSLP mRNA and protein in NHEKs in a dose-dependent manner as previously reported [21,22] ( Fig. 3a and b).…”

Section: Tslp Is Similarly Located With Tnf-a In the Ad Epidermissupporting

confidence: 77%

“…Recent studies have revealed that TSLP expression is induced by TNF-a, synthetic double-stranded RNA poly (I:C), FSL-1, flagellin, kallikrein 5, and UVB in epidermal keratinocytes [6,21,31,32]. In AD, TNF-a is released by infiltrating mast cells, T-helper lymphocytes and epidermal keratinocytes [33].…”

Section: Discussionmentioning

confidence: 99%

“…The representative inflammatory cytokine TNF-a has been reported to induce TSLP expression in keratinocytes [21,22], and also thought to be a key regulator of inflammation in AD lesions [27][28][29]. Therefore, we focused on TSLP and TNF-a expression in epidermal keratinocytes of AD lesions.…”

Section: Tslp Is Similarly Located With Tnf-a In the Ad Epidermismentioning

confidence: 99%

“…In epidermal keratinocytes, TNF-a induces the expression of TNF-a itself, IL-1a, IL-6, IL-8, IL-33, and IL-36, and these inflammatory cytokines and chemokines greatly affect the pathophysiology of inflammatory skin diseases including AD and psoriasis [14][15][16][17][18][19][20]. Of note, TNF-a also induces TSLP expression in human keratinocytes [21,22].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dexamethasone but not tacrolimus suppresses TNF-α-induced thymic stromal lymphopoietin expression in lesional keratinocytes of atopic dermatitis model

Mizuno

Morizane

Takiguchi

et al. 2015

Journal of Dermatological Science

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Section: Tslp Is Similarly Located With Tnf-a In the Ad Epidermissupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Tslp Is Similarly Located With Tnf-a In the Ad Epidermismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dexamethasone but not tacrolimus suppresses TNF-α-induced thymic stromal lymphopoietin expression in lesional keratinocytes of atopic dermatitis model

Mizuno

Morizane

Takiguchi

et al. 2015

Journal of Dermatological Science

View full text Add to dashboard Cite

“…In normal human bronchial epithelial cells, two TSLP splice variants have been reported and lfTSLP, but not sfTSLP, was highly induced after exposure to polyinosinic-polycytidylic acid (polyI:C)20. Moreover, in primary human keratinocytes, toll-like receptor ligands, a pro-inflammatory cytokine (TNF-α), and Th2 cytokines (IL-4 and IL-13) predominantly upregulate gene expression of lfTSLP, but not sfTSLP21. Another study found that synthetic sfTSLP exerts potent antimicrobial activity and that sfTSLP is the predominant form of TSLP, being the form widely and constitutively expressed in keratinocytes and saliva at steady state, both at the mRNA and protein levels22.…”

mentioning

confidence: 99%

Distinct roles of short and long thymic stromal lymphopoietin isoforms in house dust mite-induced asthmatic airway epithelial barrier disruption

Dong

Liu

et al. 2016

Sci Rep

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Loss of airway epithelial integrity contributes significantly to asthma pathogenesis. Thymic stromal lymphopoietin (TSLP) may have dual immunoregulatory roles. In inflammatory disorders of the bowel, the long isoform of TSLP (lfTSLP) promotes inflammation while the short isoform (sfTSLP) inhibits inflammation. We hypothesize that lfTSLP contributes to house dust mite (HDM)-induced airway epithelial barrier dysfunction and that synthetic sfTSLP can prevent these effects. In vitro, airway epithelial barrier function was assessed by monitoring transepithelial electrical resistance, fluorescent-dextran permeability, and distribution of E-cadherin and β-catenin. In vivo, BALB/c mice were exposed to HDM by nasal inhalation for 5 consecutive days per week to establish an asthma model. sfTSLP and 1α,25-Dihydroxyvitamin D3 (1,25D3) were administered 1 h before HDM exposure. After 8 weeks, animal lung function tests and pathological staining were performed to evaluate asthma progression. We found that HDM and lfTSLP impaired barrier function. Treatment with sfTSLP and 1,25D3 prevented HDM-induced airway epithelial barrier disruption. Moreover, sfTSLP and 1,25D3 treatment ameliorated HDM-induced asthma in mice. Our data emphasize the importance of the different expression patterns and biological properties of sfTSLP and lfTSLP. Moreover, our results indicate that sfTSLP and 1,25D3 may serve as novel therapeutic agents for individualized treatment of asthma.

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Skin‐derived TSLP stimulates skin migratory dendritic cells to promote the expansion of regulatory T cells

2023

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Therapeutic strategies that enhance regulatory T (Treg) cell proliferation or suppressive function hold promise for the treatment of autoimmune and inflammatory diseases. We previously reported that the topical application of the vitamin D3 analog MC903 systemically expands Treg cells by stimulating the production of thymic stromal lymphopoietin (TSLP) from the skin. Using mice lacking TSLP receptor expression by dendritic cells (DCs), we hereby show that TSLP receptor signaling in DCs is required for this Treg expansion in vivo. Topical MC903 treatment of ear skin selectively increased the number of migratory DCs in skin‐draining lymph nodes (LNs) and upregulated their expression of co‐stimulatory molecules. Accordingly, DCs isolated from skin‐draining LNs but not mesenteric LNs or spleen of MC903‐treated mice showed an enhanced ability to promote Treg proliferation, which was driven by co‐stimulatory signals through CD80/CD86 and OX40 ligand. Among the DC subsets in the skin‐draining LNs of MC903‐treated mice, migratory XCR1−CD11b+ type 2 and XCR1−CD11b− double negative conventional DCs promoted Treg expansion. Together, these data demonstrate that vitamin D3 stimulation of skin induces TSLP expression, which stimulates skin migratory DCs to expand Treg cells. Thus, topical MC903 treatment could represent a convenient strategy to treat inflammatory disorders by engaging this pathway.

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Long TSLP transcript expression and release of TSLP induced by TLR ligands and cytokines in human keratinocytes

Cited by 81 publications

References 30 publications

Dexamethasone but not tacrolimus suppresses TNF-α-induced thymic stromal lymphopoietin expression in lesional keratinocytes of atopic dermatitis model

Dexamethasone but not tacrolimus suppresses TNF-α-induced thymic stromal lymphopoietin expression in lesional keratinocytes of atopic dermatitis model

Distinct roles of short and long thymic stromal lymphopoietin isoforms in house dust mite-induced asthmatic airway epithelial barrier disruption

Skin‐derived TSLP stimulates skin migratory dendritic cells to promote the expansion of regulatory T cells

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