Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency.
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.
Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. tkawa@yamanashi.ac.jp
Tatsuyoshi
T
Kawamura
Youichi
Y
Ogawa
Yuumi
Y
Nakamura
Satoshi
S
Nakamizo
Yoshihiro
Y
Ohta
Hajime
H
Nakano
Kenji
K
Kabashima
Ichiro
I
Katayama
Schuichi
S
Koizumi
Tatsuhiko
T
Kodama
Atsuhito
A
Nakao
Shinji
S
Shimada
D000169:Acrodermatitis / Q000178:diet therapy / Q000473:pathology* / Q000503:physiopathology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000178:diet therapy / Q000473:pathology* / Q000503:physiopathology*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015032:Zinc / Q000172:deficiency*
D018925:Chemokines; D053773:Transforming Growth Factor beta1; D000255:Adenosine Triphosphate; D015032:Zinc