Interleukin-29 induces epithelial production of CXCR3A ligands and T-cell infiltration

Psoriasis is considered as a model for chronic immune-mediated disorders. th17-cells are pivotal players in those diseases. recently, we demonstrated that th17-cells produce interleukin (il)-29 and that il-29 is highly present in psoriatic lesions. whether il-29, with its action on epithelial cells and melanocytes, contributes to psoriasis pathogenesis, was unknown so far. analysis of il-29-treated human keratinocytes revealed induction of the chemokines cxcl10, cxcl11, and, to a much lesser extent, cxcl9. unlike these cxcr3a ligands, known to attract th1-, cd8+, nk-, and th1/th17 transient cells, no influence was found on chemokines attracting other immune cell populations or on molecules modulating the cxcr3a/cxcr3a ligand interaction. cxcr3a ligand expression was also induced by il-29 in melanocytes and in epidermis models and explanted skin. regarding other psoriasis-relevant cytokines, interferon-γ and, less potently, tumor necrosis factor-α and il-1β shared and strengthened il-29’s capacity. murine il-29 counterpart injected into mouse skin provoked local cxcl10 and cxcl11 expression, t-cell infiltration, and, in consequence, skin swelling. the elevated il-29 expression in psoriatic lesions was associated with upregulation of cxcr3a ligands compared to non-lesional skin of these patients and to the skin of healthy donors and atopic dermatitis patients, which lack il-29 production. importantly, neutralization of il-29 reduced cxcr3a ligand levels in explant cultures of psoriatic lesions. finally, elevated blood cxcl11 levels were found in psoriasis that might be useful for monitoring lesional activity of the il-29 axis. in summary, the th17-cytokine il-29 induces specific chemokines and, in consequence, provokes skin infiltration of potentially pathogenic t-cells.