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Rethinking the role of tumour necrosis factor‐α in ultraviolet (UV) B‐induced immunosuppression: altered immune response in UV‐irradiated TNFR1R2 gene‐targeted mutant mice
Author(s) -
Amerio P.,
Toto P.,
Feliciani C.,
Suzuki H.,
Shivji G.,
Wang B.,
Sauder D.N.
Publication year - 2001
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2001.04181.x
Subject(s) - immunosuppression , immune system , cancer research , ultraviolet b , tumor necrosis factor alpha , mutant , immunology , gene , alpha (finance) , medicine , biology , genetics , dermatology , construct validity , nursing , patient satisfaction
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)‐α. TNF‐α produces morphological changes in Langerhans cells indistinguishable from those induced by UVB exposure and antibodies against TNF‐α have been demonstrated to inhibit UVB‐induced immunosuppression in vivo . Objectives To clarify further the role of TNF‐α 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‐α. 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‐α. 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‐α signalling is only partially involved in UVB‐induced immunosuppression and does not play a major part in the cis ‐UCA immunosuppression mechanism.