title: Rethinking the role of tumour necrosis factor-alpha in ultraviolet (UV) B-induced immunosuppression: altered immune response in UV-irradiated TNFR1R2 gene-targeted mutant mice.
abstract: BACKGROUND
  Ultraviolet (UV) B-induced immunosuppression, implicated in the pathogenesis of skin cancers, is postulated to be mediated in part by cis-urocanic acid (cis-UCA) via tumour necrosis factor (TNF)-alpha. TNF-alpha produces morphological changes in Langerhans cells indistinguishable from those induced by UVB exposure and antibodies against TNF-alpha have been demonstrated to inhibit UVB-induced immunosuppression in vivo.
  
  
  OBJECTIVE
  To clarify further the role of TNF-alpha in UVB-induced immunosuppression and in cis-UCA immunosuppression.
  
  
  METHODS
  We performed a contact hypersensitivity (CHS) assay on gene-targeted mutant mice (TNFR1R2-/-) lacking genes for both receptors (p55 and p75) for TNF-alpha. Mice were either irradiated with UVB or injected intradermally with cis-UCA, sensitized with 2,4-dinitrofluorobenzene, challenged on the ears and the response was measured.
  
  
  RESULTS
  The TNFR1R2-/- mice showed hyporesponsiveness in the CHS response compared with wild-type (P < 0.001), confirming the proinflammatory role of TNF-alpha. However, significant suppression of CHS was seen after irradiation and after cis-UCA injection in both locally (sensitization on irradiated site; P < 0.05) and systemically (sensitization on non-irradiated site; P < 0.05) sensitized wild-type and gene-targeted mice.
  
  
  CONCLUSIONS
  These results demonstrate that TNF-alpha signalling is only partially involved in UVB-induced immunosuppression and does not play a major part in the cis-UCA immunosuppression mechanism.
authors.affiliation: Sunnybrook Health Science Center, University of Toronto, Toronto, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Amerio
authors.forename: P
authors.initials: P
authors.lastname: Toto
authors.forename: C
authors.initials: C
authors.lastname: Feliciani
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: G
authors.initials: G
authors.lastname: Shivji
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: D N
authors.initials: DN
authors.lastname: Sauder
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology / Q000528:radiation effects*; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D014560:Urocanic Acid