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 cell 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., neurofilament expression) in cultured thymic epithelial cells that are characterized by a cytokeratin-positive epithelial cell background. The proliferation 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 bipotential neuropoietic and lymphopoietic cytokines ciliary neurotrophic factor and interleukin-6. These cytokines also enhance the neuronal phenotype of thymic epithelial cells. Therefore, EGF appears to be a composite autocrine/paracrine neuromodulator in thymic stroma. This suggests that EGF may regulate thymus-dependent immune functions by promoting neuronal gene expression in neural crest-derived cells.
Screpanti
I
I
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Scarpa
S
S
Meco
D
D
Bellavia
D
D
Stuppia
L
L
Frati
L
L
Modesti
A
A
Gulino
A
A
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines / Q000502:physiology*; D017931:DNA Primers / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000502:physiology; D007633:Keratins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology*
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D017931:DNA Primers; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D007633:Keratins; D066246:ErbB Receptors