Mechanism of HBD-3 deficiency in atopic dermatitis.
Extrinsic atopic dermatitis (EAD) and intrinsic atopic dermatitis (IAD) patients suffer from recurrent bacterial and viral infections. In this study, we demonstrate significantly decreased expression of human beta defensin (HBD)-3, a potent antimicrobial peptide (AMP), in lesional skin of both IAD (p<0.01) and EAD patients (p<0.01), as compared to psoriasis patients. Using primary keratinocytes from EAD and IAD patients, we determined that the deficiency in HBD-3 expression is an acquired rather than a constitutive defect. Furthermore, we demonstrate the down-regulatory effect of IL-4, IL-10, and IL-13 - which are over-expressed in the skin of AD patients - on HBD-3 expression in keratinocytes. Additionally, treatment of EAD skin explants with antibodies against IL-4, IL-10, and IL-13 augmented the expression of HBD-3. These studies suggest that neutralizing the Th2 cytokine milieu in AD skin may augment the innate immune response against bacterial and viral pathogens.
Howell
Michael D
MD
Division of Allergy and Immunology, Department of Pediatrics, The National Jewish Medical and Research Center, Room K926, 1400 Jackson Street, Denver, CO 80206, USA.
Boguniewicz
Mark
M
Pastore
Saveria
S
Novak
Natalija
N
Bieber
Thomas
T
Girolomoni
Giampiero
G
Leung
Donald Y M
DY
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D023083:beta-Defensins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; C422950:DEFB103A protein, human; D018836:Inflammation Mediators; D023083:beta-Defensins