EPIDERMAL GROWTH-FACTOR PROMOTES A NEURAL PHENOTYPE IN THYMIC EPITHELIAL-CELLS AND ENHANCES NEUROPOIETIC CYTOKINE EXPRESSION

Neural crest-derived cells populate the thymus, and their coexistence with epithelial cells is required for proper organ development and T c ell education function. We show here that epidermal growth factor (EGF ), a major epithelial cell growth-enhancing agent, has a morphogenetic action to promote the expression of a neuronal phenotype (e.g., neuro filament expression) in cultured thymic epithelial cells that are char acterized by a cytokeratin-positive epithelial cell background. The pr oliferation of such neurodifferentiated cells is also enhanced by EGF. Furthermore, the growth factor enhances cells that express the genes encoding the preprotachykinin A-generated neuropeptides and the bipote ntial neuropoietic and lymphopoietic cytokines ciliary neurotrophic fa ctor and interleukin-6. These cytokines also enhance the neuronal phen otype of thymic epithelial cells. Therefore, EGF appears to be a compo site autocrine/paracrine neuromodulator in thymic stroma. This suggest s that EGF may regulate thymus-dependent immune functions by promoting neuronal gene expression in neural crest-derived cells.