Chemokine responses distinguish chemical-induced allergic from irritant skin inflammation: Memory T cells make the difference

Meller, Stephan; Lauerma, Antti; Kopp, Frank; Winterberg, Franziska; Anthoni, Minna; Müller, Anja; Gombert, Michael; Haahtela, Anna; Alenius, Harri; Rieker, Juliane; Dieu-Nosjean, Marie-Caroline; Kubitza, Robert; Gleichmann, Ernst; Ruzicka, Thomas; Zlotnik, Albert; Homey, Bernhard

doi:10.1016/j.jaci.2006.12.654

Cited by 64 publications

(62 citation statements)

References 41 publications

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“…However, ICD is thought to be mediated via T cell-independent innate immunity, because the ear swelling response to CrO is similar for both athymic and normal mice and neutrophils are the predominant cells in ICD (31). Recent work has shown that different patterns of inflammatory chemokines may distinguish between ACD and ICD (32). To explore such mechanisms for increased ICD in Zn deficiency, we first analyzed gene expression profiles for 44 chemokines in epidermal sheets obtained from ZA and ZD mice 24 hours after vehicle or CrO exposure.…”

Section: Dietary Zn Deficiency Causes Severe and Prolonged Irritant Cmentioning

confidence: 99%

Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency

Kawamura

Ogawa²,

Nakamura³

et al. 2012

J. Clin. Invest.

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Zinc deficiency can be an inherited disorder, in which case it is known as acrodermatitis enteropathica (AE), or an acquired disorder caused by low dietary intake of zinc. Even though zinc deficiency diminishes cellular and humoral immunity, patients develop immunostimulating skin inflammation. Here, we have demonstrated that despite diminished allergic contact dermatitis in mice fed a zinc-deficient (ZD) diet, irritant contact dermatitis (ICD) in these mice was more severe and prolonged than that in controls. Further, histological examination of ICD lesions in ZD mice revealed subcorneal vacuolization and epidermal pallor, histological features of AE. Consistent with the fact that ATP release from chemically injured keratinocytes serves as a causative mediator of ICD, we found that the severe ICD response in ZD mice was attenuated by local injection of soluble nucleoside triphosphate diphosphohydrolase. In addition, skin tissue from ZD mice with ICD showed increased levels of ATP, as did cultured wild-type keratinocytes treated with chemical irritants and the zinc-chelating reagent TPEN. Interestingly, numbers of epidermal Langerhans cells (LCs), which play a protective role against ATP-mediated inflammatory signals, were decreased in ZD mice as well as samples from ZD patients. These findings suggest that upon exposure to irritants, aberrant ATP release from keratinocytes and impaired LC-dependent hydrolysis of nucleotides may be important in the pathogenesis of AE.

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Section: Dietary Zn Deficiency Causes Severe and Prolonged Irritant Cmentioning

confidence: 99%

Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency

Kawamura

Ogawa²,

Nakamura³

et al. 2012

J. Clin. Invest.

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“…In sensitized individuals, the immune reaction is initiated by skin-infiltrating hapten-reactive CD8 + T lymphocytes, which are very efficient in inducing keratinocyte apoptosis, resulting in e-cadherin cleavage and spongiosis (3)(4)(5)(6). Effector CD4 + T lymphocytes, which outnumber CD8 + T cells in ACD skin, also contribute to disease expression, being the major source of proinflammatory cytokines that promote the activation of resident cells (7,8). Keratinocytes are not only the primary target cells for cytotoxic skin lymphocytes, but they actively regulate the magnitude of the immune response by releasing a variety of chemotactic factors which affect the quality of the lymphocytic infiltrate.…”

Section: Cd56mentioning

confidence: 99%

CD56highCD16−CD62L− NK Cells Accumulate in Allergic Contact Dermatitis and Contribute to the Expression of Allergic Responses

Carbone

Nasorri

Pennino

et al. 2009

The Journal of Immunology

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Allergic contact dermatitis is a common disease caused by an exaggerated T cell-mediated immune response to skin-applied haptens. We show in this study that NK cells affect skin immune responses to haptens by releasing type 1 cytokines and inducing keratinocytes apoptosis. Immunohistochemical stainings demonstrated that NK lymphocytes constitute ∼10% of the inflammatory infiltrate mostly distributed in the superficial dermis and in the epidermis at the site of intense spongiotic changes. More than 90% of NK cells isolated from allergic contact dermatitis skin showed a CD3-CD56highCD16− phenotype by FACS analysis. In addition, they uniformly expressed NKG2A, intermediate to high levels of perforin, and the activating receptors, NKG2D, NKp44, and NKp46, but lacked NKp30 and killer Ig-related receptors. Skin NK lymphocytes displayed a CXCR3+CCR6+CCR5+ chemokine receptor asset for homing into inflamed skin, but not CD62L and CCR7 for lymph node homing. When NK cells from nickel-allergic donors were exposed in vitro to the metal, they failed to proliferate, to upregulate CD69, and to release IFN-γ, thus indicating that NK lymphocytes do not exhibit memory-like properties to haptens. However, IL-2 released by hapten-driven T lymphocytes rapidly induced the release of IFN-γ by NK cells and promoted the NK-mediated apoptosis of autologous keratinocytes in a hapten-independent manner. Our findings underline the importance of the interaction between innate and adaptive immune mechanisms for amplification of skin allergic responses to haptens and full expression of allergic contact dermatitis

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“…Chemicals that promote allergic dermatitis tend to induce a specific cytokine profile wherein T-cell chemotactic (CXCR3) chemokines such as CXCL10 are induced (Flier et al, 1999;Meller et al, 2007). However, classifying and predicting the inflammatory response elicited by irritants is less cut and dry.…”

Section: Introductionmentioning

confidence: 99%

IL-6 deficiency exacerbates skin inflammation in a murine model of irritant dermatitis

Lee

Mickle-Kawar

Gallucci

2012

Journal of Immunotoxicology

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Chemokine responses distinguish chemical-induced allergic from irritant skin inflammation: Memory T cells make the difference

Cited by 64 publications

References 41 publications

Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency

Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency

CD56highCD16−CD62L− NK Cells Accumulate in Allergic Contact Dermatitis and Contribute to the Expression of Allergic Responses

IL-6 deficiency exacerbates skin inflammation in a murine model of irritant dermatitis

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