title: Macrophage inflammatory protein 3alpha deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Evaluate the level of MIP-3alpha in AD skin and its role in the innate immune response to vaccinia virus (VV).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Byung Eui
authors.initials: BE
authors.lastname: Kim
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Streib
authors.forename: Kevin
authors.initials: K
authors.lastname: Kisich
authors.forename: Mark
authors.initials: M
authors.lastname: Boguniewicz
authors.forename: Qutayba A
authors.initials: QA
authors.lastname: Hamid
authors.forename: Michael D
authors.initials: MD
authors.lastname: Howell
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology; D012867:Skin / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins