Interleukin-33 affects cytokine production by keratinocytes in vitiligo

Background Vitiligo is an acquired skin pigmentation disorder. Interleukin (IL)-33 is a newly described member of the IL-1 family. Aim To examine the role of IL-33 and its regulation in vitiligo. Methods Expression of IL-33 and its receptor (interleukin 1 receptor-like 1 protein; also known as ST2), in skin biopsies taken from healthy subjects and patients with vitiligo, was examined by immunofluorescence staining and western blotting. IL-33 secretion from primary keratinocytes was measured by ELISA. IL-33-stimulated release of stem cell factor (SCF), basic fibroblast growth factor (bFGF), IL-6 and tumour necrosis factor (TNF)-α from primary keratinocytes was examined by ELISA. Results IL-33 and ST2 expression was increased in lesional skin, and serum IL-33 was raised in patients with vitiligo. IL-33 expression moved from the nucleus to the cytoplasm of keratinocytes. IL-33 reduced expression of both SCF and bFGF, but increased expression of both IL-6 and TNF-α expression in primary keratinocytes. Conclusions IL-33 is secreted by keratinocytes and functions as an alarmin. It may induce melanocyte death by regulating cytokines in the cellular microenvironment.