Expression of Neurotrophic Factors and Neuropeptide Receptors by Langerhans Cells and the Langerhans Cell-Like Cell Line XS52: Further Support for a Functional Relationship Between Langerhans Cells and Epidermal Nerves

• Published in: Journal of investigative dermatology Vol. 109; no. 4; pp. 586 - 591
• Main Authors: Torii, Hideshi, Yan, Zengmin, Hosoi, Junichi, Granstein, Richard D.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-10-1997; Nature Publishing
• Subjects: Animals; Biological and medical sciences; Cell Differentiation; Cell Line; dendritic cells; Epidermis - innervation; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - immunology; Fundamental and applied biological sciences. Psychology; IL-6; Immune Sera - pharmacology; Interleukin-6 - genetics; Interleukin-6 - immunology; Interleukin-6 - metabolism; Langerhans Cells - metabolism; Mice; Mice, Inbred BALB C; mouse; Nerve Growth Factors - genetics; Nerve Growth Factors - immunology; Nerve Growth Factors - metabolism; Nervous System Physiological Phenomena; Neural Inhibition; Neurites - drug effects; Neurites - physiology; PC12 Cells - pathology; PC12 Cells - physiology; Rats; Receptors, Neuropeptide - metabolism; RNA, Messenger - metabolism; Vertebrates: skin, associated glands, phaneres, light organs, various exocrine glands (salt gland, uropygial gland...), adipose tissue, connective tissue; mouse; IL-6; dendritic cells; Neurotrophic factor; Antigen presentation; Neuron; Langerhans cell; Epidermis; Cell differentiation; Neuropeptide; Biological receptor
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12337516

Epidermal Langerhans cells are frequently anatomically associated with calcitonin gene-related peptide-containing nerves. Furthermore, calcitonin gene-related peptide inhibits Langerhans cells antigen-presenting function in several assays. Studies were performed to further explore the hypothesis that Langerhans cells and nerves have a functional relationship. To examine whether Langerhans cells may produce factors that influence nerve cell differentiation, we utilized the Langerhans cell-like cell line XS52 as a surrogate for Langerhans cells and compared it with Langerhans cells enriched to 90%. Supernatants conditioned by lipopolysaccharide-stimulated XS52 cells were able to induce the differentiation of the pheochromocytoma line PC12 into sympathetic neuron-like cells. This was also the case with enriched Langerhans cells stimulated by lipopolysaccharide. Pre-treatment of conditioned supernatants with specific neutralizing anti-sera indicated that most of the differentiation-inducing activity was due to interleukin-6 and a small amount was due to nerve growth factor and basic fibroblast growth factor. By reverse transcriptase polymerase chain reaction, three clones of the XS52 cell line, XS52-4D, XS52-11D, and XS52-8B, were found to express mRNA for interleukin-6 and expression was markedly augmented by lipopolysaccharide. mRNA for nerve growth factor and basic fibroblast growth factor was detected in XS52-4D and XSS2-11D, but not in XS52-8B. The expression of these neurotrophic factors by enriched Langerhans cells was quite similar to that of XS52-4D. In order to examine whether Langerhans cells may express receptors for nerve-derived peptides, reverse transcriptase polymerase chain reaction was employed to look for pituitary adenylate cyclase activating polypeptide type I, type II, and type III, and gastrin-releasing peptide receptors. These results suggest bidirectional signalling between Langerhans cells and nerves; nerve cells may regulate Langerhans cell function by elaboration of certain neuropeptides whereas by elaboration of interleukin-6 and, possibly, other factors.