Irritant dermatitis, irritancy and its role in allergic contact dermatitis

Smith, Harvey R.; Basketter, David A.; McFadden, John

doi:10.1046/j.1365-2230.2002.00997.x

Cited by 138 publications

(101 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Damaged cells are known to release ATP into the extracellular environment (10), and we hypothesize that the release of ATP from keratinocytes after injury or irritation of the skin leads to ATP-induced up-regulation of LC function as a homeostatic protective mechanism. This observation may also explain why contact allergens are invariably also contact irritants; irritation may be necessary for up-regulation of APC function and subsequent induction of immunity to the allergen (20). In this regard, purinergic agonists may represent a class of danger signals that alert the immune system to dying cells in a manner analogous to that recently proposed for uric acid (21).…”

Section: Discussionmentioning

confidence: 86%

Augmentation of Cutaneous Immune Responses by ATPγS: Purinergic Agonists Define a Novel Class of Immunologic Adjuvants

Granstein

Ding

Huang

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Extracellular nucleotides activate ligand-gated P2XR ion channels and G protein-coupled P2YRs. In this study we report that intradermal administration of ATPγS, a hydrolysis-resistant P2 agonist, results in an enhanced contact hypersensitivity response in mice. Furthermore, ATPγS enhanced the induction of delayed-type hypersensitivity to a model tumor vaccine in mice and enhanced the Ag-presenting function of Langerhans cells (LCs) in vitro. Exposure of a LC-like cell line to ATPγS in the presence of LPS and GM-CSF augmented the induction of I-A, CD80, CD86, IL-1β, and IL-12 p40 while inhibiting the expression of IL-10, suggesting that the immunostimulatory activities of purinergic agonists in the skin are mediated at least in part by P2Rs on APCs. In this regard, an LC-like cell line was found to express mRNA for P2X1, P2X7, P2Y1, P2Y2, P2Y4, P2Y9, and P2Y11 receptors. We suggest that ATP, when released after trauma or infection, may act as an endogenous adjuvant to enhance the immune response, and that P2 agonists may augment the efficacy of vaccines.

show abstract

Section: Discussionmentioning

confidence: 86%

Augmentation of Cutaneous Immune Responses by ATPγS: Purinergic Agonists Define a Novel Class of Immunologic Adjuvants

Granstein

Ding

Huang

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The release of TNF-a by KC is induced during allergic contact dermatitis [19,[38][39][40]. Exposure to contact allergens results in secretion of IL-1b by LC which in turn stimulates epidermal KC to secrete TNF-a, and also IL-18 [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

“…We propose that dermis-derived cells play a role in creating a directional chemotactic gradient between the epidermis and the dermis, by secreting chemokines in response to epidermis-derived cytokines (e.g. TNF-a).The release of TNF-a by KC is induced during allergic contact dermatitis [19,[38][39][40]. Exposure to contact allergens results in secretion of IL-1b by LC which in turn stimulates epidermal KC to secrete TNF-a, and also .…”

mentioning

confidence: 99%

CXCL12 is essential for migration of activated Langerhans cells from epidermis to dermis

et al. 2008

View full text Add to dashboard Cite

The initial step in Langerhans cell (LC) migration from the epidermis to the lymph node involves migration of maturing LC into the dermis. Here, we investigated the migration of LC out of the epidermis after exposure of the skin to contact allergens. Ex vivo intact human skin, epidermal sheets, and LC derived from the MUTZ-3 cell line (MUTZ-LC) were used to determine whether dermal fibroblasts play a role in mediating LC migration towards the dermis. Exposure of epidermal sheets or MUTZ-LC to allergens (nickel sulphate, 2,4-dinitrochlorobenzene, and cinnamaldehyde) or a cytokine maturation cocktail resulted in LC migration towards dermal fibroblasts. This was due to upregulation of CXCR4 on maturing LC and secretion of CXCL12/stromal derived factor-1 chemokine by fibroblasts. Neutralizing antibodies to either CXCL12 or CXCR4 completely blocked migration. Injection of CXCL12 neutralizing antibodies into intact human skin totally inhibited LC migration into the dermis. In contrast, neutralizing antibodies to CCL19/ CCL21 did not inhibit migration into the dermis. We describe a novel and essential role of dermis-derived CXCL12 in initiating migration of maturing human LC to the dermis thus permitting their further journey to the draining lymph nodes.Key words: Allergy . Chemotaxis . Cytokines . DC . Skin See accompanying commentary by Villablanca and Rodrigo IntroductionHuman skin is the external barrier to harmful environmental factors. Upon environmental assault (e.g. exposure to pathogens or allergens), Langerhans cells (LC) residing in the epidermis start to mature and migrate through the dermis [1,2]. Pathogenor allergen-exposed LC then migrate further into the afferent lymphatics towards the local lymph node where they are able to initiate a T-cell-mediated response [3]. LC migration is regulated by the sequential and differential expression of chemokines and their receptors [4,5]. Although migration to the lymph node is well documented, the chemokine ligands/receptors involved in the initial step of human LC migration out of the epidermis and into the dermis are as yet unknown.Several studies describe an essential role of CCR7 in mediating migration of mature LC towards the lymphatics [6][7][8][9][10]. CCR7 is highly expressed on fully mature, but not on immature LC, and is the chemokine receptor for the ligands CCL19 (MIP-3b) and CCL21 (6Ckine) [11][12][13]. Both of these chemokines are upregulated by lymphatic endothelial cells in response to allergen exposure [14]. Simultaneously, the chemokine receptor CCR6 on LC is downregulated upon maturation [15]. CCR6 is the receptor for CCL20 , which is mainly produced by keratinocytes (KC) in clinically normal human skin. CCR6/CCL20 is thought to 3050be of importance for epidermal homeostasis and homing of immature LC [16][17][18][19]. Taken together these reports show that loss of CCR6 and gain of CCR7 play important roles in the migration of mature LC out of the epidermis and into the lymphatic vessels. However, it is probable that other as yet unidentified sig...

show abstract

“…These pathological changes may be associated with the release of danger signals, including MSU. Smith et al [24] proposed that irritancy plays a crucial role in the development of allergic contact dermatitis. Consistent with this hypothesis, we propose that skin damage could play a crucial role in the development and deterioration of allergic skin diseases.…”

Section: Discussionmentioning

confidence: 99%

The Endogenous Danger Signal Uric Acid Augments Contact Hypersensitivity Responses in Mice

Liu¹,

Inoue²,

Nakayama

et al. 2007

Pathobiology

View full text Add to dashboard Cite

Objective: The danger hypothesis proposes that the immune system responds not only to foreign antigens but also to damaged cells or tissues. Recently, uric acid crystals (monosodium urate, MSU) from necrotic cell lysates were identified as a danger signal for dendritic cells (DCs). Our aim was to determine whether MSU modulates immune responses in the skin. Method: We analyzed the effect of MSU on trinitrochlorobenzene-induced contact hypersensitivity responses using BALB/c mice administered potassium oxonate, an uricase inhibitor, to prevent MSU degradation. Ear swelling response after elicitation and activation profiles of DCs and T cells in draining lymph nodes after sensitization were assessed. Results: Intradermal administration of MSU augmented the ear swelling response in potassium oxonate-administered mice and enhanced expression of CD86 and CD40 molecules on DCs in the lymph nodes. Activation of DCs was followed by an increase in CD69+ and CD44+ T cells in CD4+ and/or CD8+ subsets in the lymph nodes 4 days after trinitrochlorobenzene sensitization. Conclusion: These observations demonstrate that MSU is an endogenous danger signal, which augments the contact hypersensitivity response in mice. MSU released from damaged skin may act as an endogenous adjuvant to augment immune response.

show abstract

Irritant dermatitis, irritancy and its role in allergic contact dermatitis

Cited by 138 publications

References 49 publications

Augmentation of Cutaneous Immune Responses by ATPγS: Purinergic Agonists Define a Novel Class of Immunologic Adjuvants

Augmentation of Cutaneous Immune Responses by ATPγS: Purinergic Agonists Define a Novel Class of Immunologic Adjuvants

CXCL12 is essential for migration of activated Langerhans cells from epidermis to dermis

The Endogenous Danger Signal Uric Acid Augments Contact Hypersensitivity Responses in Mice

Contact Info

Product

Resources

About