Monocytes have recently been recognized as a precursor of Langerhans cells. This study examined the regulatory influence of the epithelial environment on the putative first step of the transition towards a Langerhans cell phenotype--the induction of CD1a antigen. The keratinocyte-derived cytokines granulocyte-macrophage-colony-stimulating factor, tumour necrosis factor-alpha, interleukin-6, and interleukin-1 beta induced CD1a expression, as did supernatants of keratinocytes extracted from inflammatory sites (periodontitis). Induction was abrogated by transforming growth factor-beta and a keratinocyte-derived interleukin-1 inhibitor. The optimal temperature for induction was 34 degrees C, not 37 degrees C. These results demonstrate that the components of the epithelial environment (cytokines and lower temperature) exert important influences, which may be part of local regulation of Langerhans cell development.