Role of tumour necrosis factor-alpha in ultraviolet B light-induced dendritic cell migration and suppression of contact hypersensitivity.

Abstract

Irradiation with ultraviolet B light (UVB) is known to suppress contact and delayed hypersensitivity response to a variety of antigens encountered within a short period following exposure. Such irradiation results in loss of Langerhans' cells and in synthesis of tumour necrosis factor-alpha (TNF-alpha) in the epidermis. In the present study the effect of broad-band (270-350 nm) and narrow-band (311-312 nm) UVB on the induction of contact hypersensitivity (CH) and on dendritic cell (DC) numbers in draining lymph nodes (DLN) of mice was examined. Broad-band UVB induced the accumulation of DC in DLN and this increase was substantially abrogated by treatment of mice with neutralizing antibody to TNF-alpha before irradiation. In addition, irradiation before sensitization with oxazolone resulted in a suppressed CH response. The suppression was negated to a considerable extent by TNF-alpha antibodies, administered before irradiation. Thus, one of the major effects of broad-band UVB is likely to be the synthesis of epidermal TNF-alpha which, in turn induces the migration of Langerhans' cells to DLN and leads to an impairment of their activity or function. Conversely narrow-band UVB did not result in an accumulation of DC in DLN or in a suppressed CH response. Such irradiation does, however, cause the isomerization from trans to cis-UCA in the epidermis. Cis-UCA has been proposed as a photoreceptor for UV and suppresses immune responses in a variety of experimental systems. Thus cis-UCA does not act through TNF-alpha induction or by influencing DC migration, and other studies indicate that histamine-like receptors in the skin may be involved.