title: Skin inflammation in RelB(-/-) mice leads to defective immunity and impaired clearance of vaccinia virus.
abstract: BACKGROUND
  Atopic dermatitis (AD) is an inflammatory skin disorder occurring in genetically predisposed individuals with a systemic T(H)2 bias. Atopic dermatitis patients exposed to the smallpox vaccine, vaccinia virus (VV), occasionally develop eczema vaccinatum (EV), an overwhelming and potentially lethal systemic infection with VV.
  
  
  OBJECTIVE
  To establish a murine model of EV and examine the effects of skin inflammation on VV immunity.
  
  
  METHODS
  The skin of RelB(-/-) mice, like that of chronic AD lesions in humans, exhibits thickening, eosinophilic infiltration, hyperkeratosis, and acanthosis. RelB(-/-) and wild-type (WT) control mice were infected with VV via skin scarification. Viral spread, cytokine levels, IgG2a responses and VV-specific T cells were measured.
  
  
  RESULTS
  Cutaneously VV-infected RelB(-/-), but not WT mice, exhibited weight loss, markedly impaired systemic clearance of the virus and increased contiguous propagation from the inoculation site. This was associated with a dramatically impaired generation of IFN-gamma-producing CD8(+) vaccinia-specific T cells along with decreased secretion of IFN-gamma by VV-stimulated splenocytes. The T(H)2 cytokines-IL-4, IL-5, IL-13, and IL-10-on the other hand, were overproduced. When infected intraperitoneally, RelB(-/-) mice generated robust T cell responses with good IFN-gamma production.
  
  
  CONCLUSIONS
  Allergic inflammation in RelB(-/-) mice is associated with dysregulated immunity to VV encountered via the skin. We speculate that susceptibility of AD patients to overwhelming vaccinia virus infection is similarly related to ineffective T cell responses.
  
  
  CONCLUSIONS
  The susceptibility of patients with AD to EV following cutaneous contact with VV is related to ineffective antiviral immune responses.
authors.affiliation: Department of Pediatrics, Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Eva-Jasmin
authors.initials: EJ
authors.lastname: Freyschmidt
authors.forename: Clinton B
authors.initials: CB
authors.lastname: Mathias
authors.forename: Daniel H
authors.initials: DH
authors.lastname: MacArthur
authors.forename: Amale
authors.initials: A
authors.lastname: Laouar
authors.forename: Manjunath
authors.initials: M
authors.lastname: Narasimhaswamy
authors.forename: Falk
authors.initials: F
authors.lastname: Weih
authors.forename: Hans C
authors.initials: HC
authors.lastname: Oettgen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000150:complications* / Q000235:genetics; D007109:Immunity / Q000235:genetics; D007074:Immunoglobulin G / Q000276:immunology; D007617:Kaposi Varicelliform Eruption / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D012867:Skin / Q000276:immunology* / Q000821:virology; D051841:Transcription Factor RelB / Q000235:genetics*; D014616:Vaccinia virus; D015431:Weight Loss / Q000235:genetics
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; C497594:Relb protein, mouse; D051841:Transcription Factor RelB