Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Anderson, Stacey E.; Beezhold, Kevin; Lukomska, Ewa; Richardson, Jodi; Long, Carrie M.; Anderson, Katie L.; Franko, Jennifer; Meade, B. Jean; Beezhold, Donald H.

doi:10.3109/1547691x.2013.835891

Cited by 14 publications

(27 citation statements)

References 40 publications

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“…Preliminary studies suggest that mouse serum albumin, cytoskeletal, and cuticular keratins are primary targets for haptenation upon dermal exposure. Results from our previous study (Anderson et al, 2013) and from the data presented here suggest that it is likely that the TDI exposure dose may play a critical role on the nature of allergic sensitization. The data from animals exposed to 4% TDI also suggest that general irritation caused by the chemical reactivity with skin may also drive such a response.…”

Section: Figmentioning

confidence: 55%

“…Previously, studies in our laboratory demonstrated that a single dermal dose of 4% TDI is sufficient to sensitize animals and promote a mixed Th 1 /Th 2 response highlighted by the cytokines IL-4, IL-5, IL-13, and IFN␥ (Anderson et al, 2013). Furthermore this dose was sufficient to promote increased serum IgE levels in these animals.…”

Section: Figmentioning

confidence: 84%

“…Animals were provided NIH-31-modified 6% irradiated rodent diet (Harlan Teklad) and filtered water ad libitum. Mice were given a single dermal dose (25 l/ear) of different concentrations (0.1% and 4%, v/v) of 2, 4-toluene diisocyanate (TDI) (Sigma Aldrich, St. Louis, MO) or acetone control using methodologies described previously (Anderson et al, 2013). Ears and the superficial parotid lymph nodes (DLN) that drain the head and ears were collected at designated time points.…”

Section: Methodsmentioning

confidence: 99%

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Toluene Diisocyanate (TDI) Disposition and Co-Localization of Immune Cells in Hair Follicles

Nayak

Hettick

Siegel

et al. 2014

Toxicological Sciences

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Diisocyanates (dNCOs) are potent chemical allergens utilized in various industries. It has been proposed that skin exposure to dNCOs produces immune sensitization leading to work-related asthma and allergic disease. We examined dNCOs sensitization by using a dermal murine model of toluene diisocyanate (TDI) exposure to characterize the disposition of TDI in the skin, identify the predominant haptenated proteins, and discern the associated antigen uptake by dendritic cells. Ears of BALB/c mice were dosed once with TDI (0.1% or 4% v/v acetone). Ears and draining lymph nodes (DLNs) were excised at selected time points between 1 h and 15 days post-exposure and were processed for histological, immunohistochemical, and proteomic analyses. Monoclonal antibodies specific for TDI-haptenated protein (TDI-hp) and antibodies to various cell markers were utilized with confocal microscopy to determine co-localization patterns. Histopathological changes were observed following exposure in ear tissue of mice dosed with 4% TDI/acetone. Immunohistochemical staining demonstrated TDI-hp localization in the stratum corneum, hair follicles, and sebaceous glands. TDI-hp were co-localized with CD11b(+) (integrin αM/Mac-1), CD207(+) (langerin), and CD103(+) (integrin αE) cells in the hair follicles and in sebaceous glands. TDI-hp were also identified in the DLN 1 h post-exposure. Cytoskeletal and cuticular keratins along with mouse serum albumin were identified as major haptenated species in the skin. The results of this study demonstrate that the stratum corneum, hair follicles, and associated sebaceous glands in mice are dendritic cell accessible reservoirs for TDI-hp and thus identify a mechanism for immune recognition following epicutaneous exposure to TDI.

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Section: Figmentioning

confidence: 55%

Section: Figmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

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Toluene Diisocyanate (TDI) Disposition and Co-Localization of Immune Cells in Hair Follicles

Nayak

Hettick

Siegel

et al. 2014

Toxicological Sciences

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“…Animals (n = 4–5) were exposed to a single dose of 0.5–4% TDI (v/v) on the dorsal surface of each ear (25 μl per ear). The highest concentration (4% v/v; the maximum sensitizing concentration with minimal toxicity) and dosing regimen was previously shown to induce sensitization (Anderson et al ., 2013) and sensitization was confirmed in the lower dose based on total serum IgE levels and dLN allergic cytokine mRNA expression (0.5% v/v; data not shown). Acetone was selected as the vehicle control to minimize chemical reactivity as diisocyanates react with OH groups which are present in other potential vehicles such as olive oil.…”

Section: Methodsmentioning

confidence: 99%

A Role for Regulatory T Cells in a Murine Model of Epicutaneous Toluene Diisocyanate Sensitization

et al. 2016

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Toluene diisocyanate (TDI) is a leading cause of chemical-induced occupational asthma which impacts workers in a variety of industries worldwide. Recently, the robust regulatory potential of regulatory T cells (Tregs) has become apparent, including their functional role in the regulation of allergic disease; however, their function in TDI-induced sensitization has not been explored. To elucidate the kinetics, phenotype, and function of Tregs during TDI sensitization, BALB/c mice were dermally exposed (on each ear) to a single application of TDI (0.5–4% v/v) or acetone vehicle and endpoints were evaluated via RT-PCR and flow cytometry. The draining lymph node (dLN) Treg population expanded significantly 4, 7, and 9 days after single 4% TDI exposure. This population was identified using a variety of surface and intracellular markers and was found to be phenotypically heterogeneous based on increased expression of markers including CD103, CCR6, CTLA4, ICOS, and Neuropilin-1 during TDI sensitization. Tregs isolated from TDI-sensitized mice were significantly more suppressive compared with their control counterparts, further supporting a functional role for Tregs during TDI sensitization. Last, Tregs were depleted prior to TDI sensitization and an intensified sensitization response was observed. Collectively, these data indicate that Tregs exhibit a functional role during TDI sensitization. Because the role of Tregs in TDI sensitization has not been previously elucidated, these data contribute to the understanding of the immunologic mechanisms of chemical induced allergic disease.

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“…While those studies evaluated the elicitation phase of the allergic response, even fewer studies have described roles for miRNA in the sensitization phase of an allergic response. Anderson et al (2014) investigated global lymph node miRNA expression profiles in a murine model of dermal TDI sensitization. Increases were observed in miR-21, miR-22, miR-155, miR-126, miR-27b, miR-210, miR-31, and miR-301a expression after a single dermal sensitizing application of TDI.…”

Section: Epigenetic Mediators Of Chemical Allergy In the Skinmentioning

confidence: 99%

Novel cutaneous mediators of chemical allergy

Shane

Long

Anderson

2019

Journal of Immunotoxicology

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Chemical allergy can manifest into allergic contact dermatitis and asthma and the importance of skin sensitization in both of these diseases is increasingly being recognized. Given the unique characteristics of chemical allergy, coupled with the distinct immunological microenvironment of the skin research is still unraveling the mechanisms through which sensitization and elicitation occur. This review first describes the features of chemical sensitization and the known steps that must occur to develop a chemical allergy. Next, the unique immunological properties of the skin -which may influence chemical sensitization -are highlighted. Additionally, mediators involved with the development of allergy are reviewed, starting with early ones -including the properties of haptens, skin integrity, the microbiome, the inflammasome, and toll-like receptors (TLR). Novel cellular mediators of chemical sensitization are highlighted, including innate lymphoid cells, mast cells, T-helper (T H ) cell subsets, and skin intrinsic populations including cd T-cells and resident memory T-cells. Finally, this review discusses two epigenetic mechanisms that can influence chemical sensitization, microRNAs and DNA methylation. Overall, this review highlights recent research investigating novel mediators of chemical allergy that are present in the skin. It also emphasizes the need to further explore these mediators to gain a better understanding of what makes a chemical an allergen, and how best to prevent the development of chemical-induced allergic diseases. ARTICLE HISTORY

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Expression kinetics of miRNA involved in dermal toluene 2,4-diisocyanate sensitization

Cited by 14 publications

References 40 publications

Toluene Diisocyanate (TDI) Disposition and Co-Localization of Immune Cells in Hair Follicles

Toluene Diisocyanate (TDI) Disposition and Co-Localization of Immune Cells in Hair Follicles

A Role for Regulatory T Cells in a Murine Model of Epicutaneous Toluene Diisocyanate Sensitization

Novel cutaneous mediators of chemical allergy

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