Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells

Allergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8(+) T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8(+) T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8(+) T cells and activation of a population of T cells identified as ICOS(+)CD4(+)Foxp3(+) Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.

Are material safety data sheets (MSDS) useful in the diagnosis and management of occupational contact dermatitis?

This study assesses both the success of medical practitioners in accessing hazardous substances' information from product manufacturers and the accuracy and clinical usefulness of Material Safety Data Sheets (MSDS) presented by workers with suspected occupational contact dermatitis (OCD). 00 consecutively presented MSDS were collected from 42 workers attending an occupational dermatology clinic. Product manufacturers were contacted to verify ingredients. MSDS were evaluated for compliance with the Australian criteria for listing of OCD relevant information (sensitizers present at a concentration > or =1%, irritants present at a concentration > or =20%), and for clinical usefulness. All sensitizers were checked for clinical relevance to the worker's dermatitis. Manufacturers supplied product constituents for 77/100 MSDS. 58 MSDS satisfied the Australian standard. 57/58 MSDS were deemed clinically useful. Irritants were listed for 19/23 MSDS and sensitizers were listed for 30/68 MSDS (P = 0.001). 3 MSDS contained sensitizers, which were clinically relevant to the presenting worker's dermatitis, 1 appropriately listed, 1 present at > or =1% but not listed, and 1 present at <1% in the product and therefore, not required to be listed. Sensitizers are frequently omitted from MSDS and clinicians are often unsuccessful in obtaining crucial information from manufacturers. MSDS are inadequate for the protection and diagnosis of workers with suspected OCD.

A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B

Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in situ hybridization and immunohistochemistry. In contrast to normal skin and psoriasis, a significant enhancement of perforin and granzyme B gene expression and immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were located in the dense perivascular infiltrate as well as at sites of marked spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion, our data suggest that T-cell-mediated mechanisms involving cytotoxic granule proteins may elicit epidermal cell injury in vivo and thereby strongly contribute to the development of allergic contact dermatitis in humans.

Cytokines and chemokines in irritant contact dermatitis

Irritant contact dermatitis is a result of activated innate immune response to various external stimuli and consists of complex interplay which involves skin barrier disruption, cellular changes, and release of proinflammatory mediators. In this review, we will focus on key cytokines and chemokines involved in the pathogenesis of irritant contact dermatitis and also contrast the differences between allergic contact dermatitis and irritant contact dermatitis.

Th17 cells and tissue remodeling in atopic and contact dermatitis

BACKGROUND: Eczematous skin lesions of atopic dermatitis (AD) as well as allergic and irritant contact dermatitis (ACD, ICD) are characterized by the same typical clinical signs, although due to different causes. In both AD and ACD, the presence of T helper 17 cells which play an important role in host defense, has been reported. Furthermore, IL-17 is involved in tissue repair and remodeling. This study aimed to investigate IL-17 expression in acute eczematous skin lesions and correlate it with markers of remodeling in AD, ACD, and ICD. METHODS: Skin specimens were taken from positive patch test reactions to aeroallergens, contact allergens, and irritants at days 2, 3, and 4. Inflammatory cells as well as the expression of cytokines and extracellular matrix proteins were evaluated by immunofluorescence staining and confocal microscopy. RESULTS: Allergic contact dermatitis and ICD were characterized by IFN-γ expression, whereas in AD lesions, IL-13 expression and high numbers of eosinophils were the prominent phenotype. Expression of IL-17, but also IL-21 and IL-22, was observed in all eczema subtypes. The number of IL-22+ T cells correlated with the number of eosinophils. Markers of remodeling such as MMP-9, procollagen-3, and tenascin C were observed in all acute eczematous lesions, while a correlation of IL-17+ T cell numbers with tenascin C-expressing cells and MMP-9+ eosinophils was apparent. CONCLUSION: The expression of IL-17 and related cytokines, such as IL-22, was demonstrated in acute eczematous lesions independent of their pathogenesis. Our results suggest a potential role for IL-17 in remodeling of the skin.

Contact dermatitis from shoes: an update

Contact dermatitis is a common inflammatory skin condition characterized by erythematous and pruritic skin lesions that occur after contact with a foreign substance. There are two forms of contact dermatitis: irritant and allergic. Irritant contact dermatitis is caused by the non–immune-modulated irritation of the skin by a substance, leading to skin changes. Allergic contact dermatitis is a delayed hypersensitivity reaction in which a foreign substance comes into contact with the skin; skin changes occur after reexposure to the substance. A medical condition referred to as “shoe dermatitis” is a form of contact dermatitis caused by the contact of the foot with parts of the shoe due to these materials. Shoe dermatitis is a diagnostic and therapeutic challenge and is a common type of contact dermatitis. It is imperative the foot and ankle physician become familiar with recognizing signs and symptoms of shoe dermatitis so that their patients can be accurately diagnosis and appropriately treated to avoid secondary infections and disability. This review will first present causative factors for the etiology of shoe contact dermatitis supported by clinical-based evidence as found in the medical literature. Secondly, a description of the signs and symptoms of shoe contact dermatitis will be presented in a narrative fashion. Finally, both treatment options and preventative measures to avoid shoe.

Transforming growth factor -beta signaling through Smad3 in allergy : Studies in the mechanisms of asthma, atopic dermatitis and allergic contact reactions

Transforming growth factor β signalling through Smad3 in allergy Allergic diseases, such as atopic dermatitis, asthma, and contact dermatitis are complex diseases influenced by both genetic and environmental factors. It is still unclear why allergy and subsequent allergic disease occur in some individuals but not in others. Transforming growth factor (TGF)-β is an important immunomodulatory and fibrogenic factor that regulates cellular processes in injured and inflamed skin. TGF-β has a significant role in the regulation of the allergen-induced immune response participating in the development of allergic and asthmatic inflammation. TGF-β is known to be an immunomodulatory factor in the progression of delayed type hypersensitivity reactions and allergic contact dermatitis. TGF-β is crucial in regulating the cellular responses involved in allergy, such as differentiation, proliferation and migration. TGF-β signals are delivered from the cytoplasm to the nucleus by TGF-β signal transducers called Smads. Smad3 is a major signal transducer in TGF-β -signalling that controls the expression of target genes in the nucleus in a cell-type specific manner. The role of TGF-β-Smad3 -signalling in the immunoregulation and pathophysiology of allergic disorders is still poorly understood. In this thesis, the role of TGF-β-Smad -signalling pathway using Smad3 -deficient knock out mice in the murine models of allergic diseases; atopic dermatitis, asthma and allergic contact reactions, was examined. Smad3-pathway regulates allergen induced skin inflammation and systemic IgE antibody production in a murine model atopic dermatitis. The defect in Smad3 -signalling decreased Th2 cytokine (IL-13 and IL-5) mRNA expression in the lung, modulated allergen induced specific IgG1 response, and affected mucus production in the lung in a murine model of asthma. TGF-β / Smad3 -signalling contributed to inflammatory hypersensitivity reactions and disease progression via modulation of chemokine and cytokine expression and inflammatory cell recruitment, cell proliferation and regulation of the specific antibody response in a murine model of contact hypersensitivity. TGF-β modulates inflammatory responses - at least partly through the Smad3 pathway - but also through other compensatory, non-Smad-dependent pathways. Understanding the effects of the TGF-β signalling pathway in the immune system and in disease models can help in elucidating the multilevel effects of TGF-β. Unravelling the mechanisms of Smad3 may open new possibilities for treating and preventing allergic responses, which may lead to severe illness and loss of work ability. In the future the Smad3 signalling pathway might be a potential target in the therapy of allergic diseases.