Kim BE, Leung DY, Streib JE et al.Macrophage inflammatory protein 3alpha deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus. J Allergy Clin Immunol 119:457-463

Inje University, Kŭmhae, Gyeongsangnam-do, South Korea
Journal of Allergy and Clinical Immunology (Impact Factor: 11.48). 02/2007; 119(2):457-63. DOI: 10.1016/j.jaci.2006.10.005
Source: PubMed


Patients with atopic dermatitis (AD) are prone to disseminated viral skin infections and therefore are not vaccinated against smallpox because of potential complications. Macrophage inflammatory protein 3alpha (MIP-3alpha) is a C-C chemokine expressed by keratinocytes that exhibits antimicrobial activity against bacteria and fungi; however, its role in antiviral innate immunity is unknown.
Evaluate the level of MIP-3alpha in AD skin and its role in the innate immune response to vaccinia virus (VV).
Macrophage inflammatory protein 3alpha levels were evaluated using real-time RT-PCR, immunodot-blot, and immunohistochemistry. The antiviral activity of MIP-3alpha was determined using a standard viral plaque assay.
Macrophage inflammatory protein 3alpha gene expression was significantly (P < .01) decreased in AD skin (0.21 +/- 0.05 ng MIP-3alpha/ng glyceraldehyde-3-phosphate dehydrogenase) compared with psoriasis skin (0.67 +/- 0.13). This was confirmed at the protein level using immunohistochemistry. We further demonstrate that T(H)2 cytokines downregulate MIP-3alpha expression. The importance of MIP-3alpha in the innate immune response against VV was established by first demonstrating that MIP-3alpha exhibits activity against VV. Second, VV replication was significantly increased (P < .01) in keratinocytes treated with an antibody to neutralize MIP-3alpha.
The current study demonstrates that MIP-3alpha exhibits antiviral activity against VV and demonstrates the importance of MIP-3alpha in the innate immune response against VV. In addition, AD skin is deficient in MIP-3alpha, in part because of the overexpression of T(H)2 cytokines in AD skin.
MIP-3alpha deficiency in AD skin contributes to patients' increased propensity toward eczema vaccinatum. Increasing MIP-3alpha or neutralizing T(H)2 cytokines could prevent adverse reactions in patients with AD after smallpox vaccination.

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Available from: Kevin O Kisich, Apr 11, 2014
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    • "Th2 polarity with excess production of Th2 cytokines (interleukin [IL]-4, IL-5 and IL-13) may be a key factor in the epithelial production of fibronectin and fibrinogen, which can act as substrates for S. aureus adherence9. There is growing evidence suggesting that this Th2 polarity may adversely affect the innate immune response in the skin of AD patients by inhibiting the productions of AMP and the antimicrobial chemokine MIP3α (CCL20)10,11. Additionally, increased levels of Th2 cytokines inhibit the keratinocyte mobilization of HBD-312. Therefore, biomarkers for Th2 polarity such as serum total immunoglobulin E (IgE) and eosinophil counts can be associated with S. aureus superinfection. "
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    ABSTRACT: Staphylococcus aureus (SA) has peculiar abilities to colonize the skin in atopic dermatitis (AD) patients. We sought to determine the colonization rates of SA in acute and chronic skin lesions of AD patients, to find any difference in colonization rates according to age and to find the influences of total immunoglobulin E (IgE) and eosinophil counts to the colonization of SA. We evaluated the total IgE level and eosinophil counts, and cultured SA from the skin lesions of 687 AD patients (131 acute and 556 chronic skin lesions) and 247 control urticaria patients (July 2009 to November 2010; Samsung Medical Center Dermatology Clinic, Seoul, Korea). The SA colonization rates were 74%, 38% and 3% in acute, chronic skin lesions and control skin, respectively, and they were increased with age in AD patients. The colonization rate in chronic skin lesions was higher in the high IgE/eosinophilia groups as compared to the normal IgE/eosinophil groups. The SA colonization rate was higher in AD patients and especially in acute lesions, and had a tendency to increase with age. As the colonization rates were only higher in the high IgE/eosinophilia groups of chronic skin lesions, we suggested that SA may invade the skin through barrier defects in acute skin lesions, but the colonization in chronic lesions may be orchestrated through many different factors.
    Annals of Dermatology 11/2013; 25(4):410-6. DOI:10.5021/ad.2013.25.4.410 · 1.39 Impact Factor
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    • "Insufficient expression and production of CCL20/MIP-3a in AD skin has been shown to increase the potential for disseminated VV infection after smallpox vaccination (Kim et al., 2007a). CCL27 is exclusively expressed by keratinocytes and selectively attracts memory T cells to the skin by interacting with its receptor CCR10 (Homey et al., 2000, 2002; Morales et al., 1999). "
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    ABSTRACT: Atopic dermatitis is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10-20 % of infants and 1-3% of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. Probably half of the children with atopic dermatitis devel- op some other form of atopic disease later in life. The pathogenesis involves a complex interplay of fac- tors including genetic predisposition due to altered immune or skin barrier function, interactions with the environment such as food and allergen exposures, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of atopic dermatitis and how insights provide new therapeutic potential for its treatment.
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