Ultraviolet B light-induced alterations in epidermal Langerhans cells are mediated in part by tumor necrosis factor-alpha.

Acute, low-dose treatment of murine skin with ultraviolet B light (UVB) impairs the induction of contact hypersensitivity to dinitrofluorobenzene, and depletes the epidermis of normally appearing class II MHC positive Langerhans cells. Recent studies with inbred strains of mice have revealed that impairment of contact hypersensitivity by UVB is a polymorphic trait that is polygenically dictated by susceptibility alleles at the Lps and Tnf alpha loci. Since impairment of contact hypersensitivity by UVB has been associated with deleterious effects on Langerhans cells, we have tested the hypotheses that UVB and TNF alpha have similar effects on epidermal Langerhans cells and that TNF alpha is an important mediator of this UVB-induced effect. Our results confirm that both UVB and TNF alpha reduce the density of class II MHC-bearing epidermal cells and alter the morphology (shortened or absent dendrites, rounded shape) of the cells that remain. UVB- and TNF alpha-induced changes are prevented by systemic administration of neutralizing anti-TNF alpha antibodies. Circumstantial evidence, based on time of onset of numerical and morphologic changes among Langerhans cells following epidermal treatment, suggests that TNF alpha is the mediator of UVB-induced changes. Moreover, the ability of intradermally injected TNF alpha to alter Langerhans cells depends, in part, on whether the strain of mouse is of the UVB-susceptible or UVB-resistant phenotype as it pertains to the effect of UVB on contact hypersensitivity.