Epicutaneous exposure to nickel induces nickel allergy in mice via a <scp>MyD88</scp>‐dependent and interleukin‐1‐dependent pathway

Vennegaard, Marie T.; Dyring‐Andersen, Beatrice; Skov, Lone; Nielsen, Morten Milek; Bzorek, Michael; Poulsen, Steen Seier; Thomsen, Allan Randrup; Woetmann, Anders; Thyssen, Jacob P.; Johansen, Jeanne Duus; Ødum, Niels; Menné, Torkil; Geisler, Carsten; Bonefeld, Charlotte M.

doi:10.1111/cod.12270

Cited by 30 publications

(29 citation statements)

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“…Both nickel and cobalt facilitate dimerization of human TLR4, thereby inducing the production of various cytokines and chemokines required for initiation of the allergic response . Furthermore, we have shown that nickel allergy can be induced in mice via an MyD88‐dependent and IL‐1‐dependent but TLR4‐independent pathway, indicating that nickel can activate the innate immune response by various mechanisms . In agreement with this, it has been shown that NiCl 2 induces NLRP3–ASC–capase‐1 inflammasome activation in APCs, resulting in IL‐1β production via mechanisms involving lysosome rupture, mitochondrial ROS, generation and cation flux .…”

Section: Effects Of Mixing Contact Allergenssupporting

confidence: 72%

“…Contact allergens can also lead to activation of the NLRP3 inflammasome, which activates caspase‐1, leading to processing of pro‐interleukin (IL)‐1β and pro‐IL‐18 to IL‐1β and IL‐18, respectively . IL1β is already induced in the skin 15 min after exposure to allergens, and plays a central role in the allergic response . Activation of the NLRP3 inflammasome by contact allergens seems to be mediated by an indirect pathway involving reactive oxygen species (ROS) and ATP .…”

Section: Immune Responses To Contact Allergens In Generalmentioning

confidence: 99%

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Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

et al. 2017

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SummaryAllergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety.Key words: fragrances; hair dyes; metals; mixtures of allergens.Contact allergy is very frequent in the European population, as shown by Diepgen et al., who found that 27% were sensitised to common allergens (1). This may lead to allergic contact dermatitis if exposure exceeds the individual threshold of response.The allergic response is frequently directed towards nickel, cobalt, fragrances, hair dye chemicals, or preservatives. Many of these molecules are categorized as weak to moderate allergens -this term will be used throughout the article for (pre/pro)haptens (2). Surprisingly, even 'weak to moderate' allergens do induce allergic contact dermatitis in many people. This indicates that exposure parameters, such as dose and exposure frequency, are critical. Interestingly, consumers are rarely exposed to one isolated allergen, but are more often exposed to mixtures of allergens, for example in the form of metal alloys, cosmetics, and cleaning agents (3, 4). The impact of being exposed to a mixture of allergens instead of a single allergen has not been well studied. Studies from our group have suggested that exposure to mixtures of allergens has a great impact on the immune responses to single allergens within the mixture. In this review, we will discuss the current knowledge on how exposure to mixtures of contact allergens affects the immune system by (i) altering the chemical properties of single allergens in the mixtures, (ii) changing the inflammatory response, and (iii) affecting T cell activation, proliferation, and differentiation. Furthermore, we will discuss other factors, such as the presence of irritants, a disrupted skin barrier, local skin inflammation, and local skin memory, that could increase the response to allergens. Finally, we will discuss the clinical impact of

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Section: Effects Of Mixing Contact Allergenssupporting

confidence: 72%

Section: Immune Responses To Contact Allergens In Generalmentioning

confidence: 99%

Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

et al. 2017

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“…However, it is not known whether these metals activate ROS/NLRP3 inflammasomes in vivo or whether this pathway is required for the generation of hypersensitivity. While IL-1R signaling has been shown to be important in murine models of nickel-induced hypersensitivity [20], release of biologically-active IL-1α is not dependent upon the inflammasome and could account for these effects [21]. For example, beryllium exposure in the lung induced rapid release of IL-1α and not IL-1β; however, after long-term exposure to beryllium, IL-1β is released [22,23].…”

Section: Recognition Of Metals By the Innate Immune Systemmentioning

confidence: 99%

Interplay of innate and adaptive immunity in metal-induced hypersensitivity

McKee

Fontenot

2016

Current Opinion in Immunology

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Metal-induced hypersensitivity is driven by T cell sensitization to metal ions. Recent advances in our understanding of the complex interactions between innate and adaptive immunity have expanded our knowledge of the pathogenesis of these diseases. Metals activate the innate immune system through direct binding to pathogen recognition receptors, activation of the inflammasome, or the induction of cellular death and release of alarmins. Certain metals can serve as adjuvants, promoting dendritic cell activation and migration as well as antigen presentation to metal-specific T cells. These T cells can recognize metals as haptens or as altered MHC-peptide complexes. The ability of metals to create these neoantigens emphasizes the similarity between metal-induced hypersensitivity and autoimmunity.

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“…Mice were sensitized with 10% NiCl 2 , 10% NiCl 2 plus 1% CoCl 2 , 10% CoCl 2 , 10% CoCl 2 plus 1% NiCl 2 in white petrolatum or vehicle (pure white petrolatum) as previously described (Fig. 1a) (9). Mice studies were performed in accordance with Danish national animal protection guidelines 3 weeks after sensitization, the mice were challenged by painting with 10% NiCl 2 , 10% CoCl 2 or vehicle (pure white petrolatum) twice with a 24-h interval.…”

Section: Experimental Designmentioning

confidence: 99%

Nickel acts as an adjuvant during cobalt sensitization

Bonefeld

Nielsen

Vennegaard

et al. 2015

Experimental Dermatology

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Metal allergy is the most frequent form of contact allergy with nickel and cobalt being the main culprits. Typically, exposure comes from metal‐alloys where nickel and cobalt co‐exist. Importantly, very little is known about how co‐exposure to nickel and cobalt affects the immune system. We investigated these effects by using a recently developed mouse model. Mice were epicutaneously sensitized with i) nickel alone, ii) nickel in the presence of cobalt, iii) cobalt alone, or iv) cobalt in the presence of nickel, and then followed by challenge with either nickel or cobalt alone. We found that sensitization with nickel alone induced more local inflammation than cobalt alone as measured by increased ear‐swelling. Furthermore, the presence of nickel during sensitization to cobalt led to a stronger challenge response to cobalt as seen by increased ear‐swelling and increased B and T cell responses in the draining lymph nodes compared to mice sensitized with cobalt alone. In contrast, the presence of cobalt during nickel sensitization only induced an increased CD8+ T cell proliferation during challenge to nickel. Thus, the presence of nickel during cobalt sensitization potentiated the challenge response against cobalt more than the presence of cobalt during sensitization to nickel affected the challenge response against nickel. Taken together, our study demonstrates that sensitization with a mixture of nickel and cobalt leads to an increased immune response to both nickel and cobalt, especially to cobalt, and furthermore that the adjuvant effect appears to correlate with the inflammatory properties of the allergen..

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Epicutaneous exposure to nickel induces nickel allergy in mice via a MyD88‐dependent and interleukin‐1‐dependent pathway

Abstract: This new model for nickel allergy that reflects epicutaneous exposure to nickel in humans shows that nickel allergy is dependent on MyD88 and IL-1 receptor signalling, but independent of TLR4.

Cited by 30 publications

References 49 publications

Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

Interplay of innate and adaptive immunity in metal-induced hypersensitivity

Nickel acts as an adjuvant during cobalt sensitization

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