Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis.
Recurrent skin infections in extrinsic atopic dermatitis (EAD) may be because of the suppression of anti-microbial peptide (AMP) expression by interleukin (IL)-4 and IL-13. Twenty to thirty percent of AD, however, are classified as intrinsic atopic dermatitis (IAD). They exhibit normal serum IgE levels, no allergen-specific sensitization, and lower levels of IL-4 and IL-13 than EAD. Both forms of AD have increased propensity to skin infection, suggesting a novel mechanism for infection in IAD. In this study, we observed significantly decreased human beta-defensin (HBD)-2 gene expression in the skin of both IAD (p = 0.010) and EAD (p = 0.004), as compared with psoriasis patients. Conversely, IAD (p = 0.019) and EAD (p = 0.002) skin lesions exhibited elevated IL-10 gene expression when compared with psoriasis. Using primary keratinocytes, we found that the deficiency in AMP expression is an acquired rather than a constitutive defect. Interestingly, neutralizing antibodies to IL-10 augmented the production of tumor necrosis factor-alpha and interferon-gamma by peripheral blood mononuclear cell from AD patients. Additionally, treatment of AD skin explants with anti-IL-10 augmented the expression of both HBD-2 and LL-37. Thus, increased levels of IL-10 may contribute to the AMP deficiency in both IAD and EAD by reducing cytokines that induce AMP.
Howell
Michael D
MD
Division of Allergy and Immunology, Department of Pediatrics, The National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Novak
Natalija
N
Bieber
Thomas
T
Pastore
Saveria
S
Girolomoni
Giampiero
G
Boguniewicz
Mark
M
Streib
Joanne
J
Wong
Cathy
C
Gallo
Richard L
RL
Leung
Donald Y M
DY
D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000502:physiology*; D018793:Interleukin-13 / Q000502:physiology; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C106641:DEFB4A protein, human; D018793:Interleukin-13; D023083:beta-Defensins; D016753:Interleukin-10; D054804:Cathelicidins