IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis

Background: IL-31 is a newly discovered T-cell cytokine that, when overexpressed in mice, results in pruritus and skin dermatitis resembling human atopic dermatitis (AD). Objective: We sought to investigate the expression of IL-31 and IL-31 receptor A (IL-31RA) in skin biopsy specimens and peripheral blood cells from patients with AD and healthy individuals. Methods: Expression of IL-31 and IL-31RA was evaluated in skin biopsy specimens from patients with AD and healthy individuals by means of immunohistochemistry and RT-PCR. IL-31 protein production by skin-homing cutaneous lymphocyte antigen (CLA)-positive T cells was also assessed. Results: IL-31RA protein was expressed by keratinocytes and infiltrating macrophages in skin biopsy specimens from patients with AD. Comparisons between skin from patients with AD and healthy skin showed IL-31RA expression at higher levels on epidermal keratinocytes in AD samples. Infiltrating cells, more numerous in skin from patients with AD compared with that of healthy individuals, expressed IL31 mRNA. Histomorphometric analysis of these cells indicated they were of the lymphocytic lineage, with the majority of cells staining positive for CLA and CD3. IL31 mRNA and protein expression is largely restricted to CD45RO(+) (memory) CLA(+) T cells in peripheral blood of patients with AD and healthy volunteers. Moreover, circulating CLA(+) T cells from patients with AD, but not from patients with psoriasis, are capable of producing I higher levels of IL-31 compared with CLA(+) T cells from healthy individuals. However, the average levels of IL-31 were not significantly different between patients with AD and healthy individuals. Conclusion: We provide evidence that IL-31 expression is associated with CLA(+) T cells and might contribute to the development of AD-induced skin inflammation and pruritus.