Thioredoxin inhibits epidermal Langerhans’ cell (LC) migration in man and mouse (44.6)

Abstract Epidermal LC play a critical role in the initiation of skin immune responses. LC migration is dependent upon cytokine signals, provided by tumour necrosis factor-α (TNF-α) and interleukin (IL)-1β. We have now examined the ability of human recombinant thioredoxin (hTrx), a redox-active protein, to influence LC migration. Wild type hTrx and various cysteine to alanine mutants were produced in E coli. LC migration in response to chemical contact allergen (oxazolone; Ox) or to intradermal (id) injection of recombinant murine TNF-α or IL-1β was assessed in BALB/c mice. LC migration was provoked in healthy human volunteers (n=10) by id injection of recombinant human TNF-α. Various forms of hTrx were administered by topical application 2h prior to the migratory stimuli. LC densities were assessed in epidermal sheets by immunofluorescent staining for MHC class II (mouse) or CD1a (human). Topical application of hTrx inhibited significantly Ox- and TNF-α-induced LC migration in BALB/c strain mice, but failed to impact on IL-1β-induced migration. Use of mutant forms of hTrx demonstrated that this ability was redox-independent. Application to the skin of wild type hTrx to human volunteers inhibited TNF-α-induced LC migration also. Inhibition of LC migration was selective for IL-1β-dependent stimuli (contact allergen and TNF-α). These data suggest that thioredoxin possesses novel immunomodulatory properties as a result of its ability to modulate IL-1β production and/or signalling.