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.
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.
Amerio
P
P
Sunnybrook Health Science Center, University of Toronto, Toronto, Ontario, Canada.
Toto
P
P
Feliciani
C
C
Suzuki
H
H
Shivji
G
G
Wang
B
B
Sauder
D N
DN
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
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