Roles for IL-1 and TNF alpha in dynamic behavioral responses of Langerhans cells to topical hapten application

Background: To understand the behavioral biology of Langerhans cells (LCs), we recently recorded time-lapse images of LCs in the knock-in mice expressing the I-A beta chain tagged with the enhanced green fluorescence protein (EGFP). EGFP(+) LCs showed relatively limited motility in the steady state, whereas topical application of dinitrofluorobenzene (DNFB) markedly augmented a unique movement of dendrites characterized by rhythmic extension and retraction, termed dSEARCH, and triggered amoeba-like lateral migration of cell bodies. Objective: To define underlying mechanisms by which hapten treatment alters LC behaviors. Methods: The I-A beta-EGFP mice received subcutaneous (s.c.) injection of recombinant IL-1 alpha or TNF alpha (50 ng/animal) and dynamic behaviors of EGFP(+) LCs were recorded by time-lapse confocal microscopy at several time points to measure their dSEARCH activities and lateral migration. In a different set of experiments, IL-1 receptor antagonist (IL-1 Ra) or soluble TNF receptor-2 (sTNFR2) (0.5 mu g/animal) was s.c. injected into the ear skin 30 min before topical application of DNFB, and LC behaviors analyzed 30 h later. Results: Local injection of IL-1 or TNF alpha induced significant, albeit modest, augmentation of both dSEARCH and lateral migration. Co-injection of TNF alpha and IL-1 alpha further exacerbated motile activities in a synergistic manner by similar magnitudes observed after DNFB application. Conversely, DNFB-induced behavioral changes were inhibited completely by local injection of IL-1Ra or sTNFR2. Conclusion: IL-1 and TNF alpha serve as equally important mediators of hapten induced alteration of LC behaviors. Motile activities of epidermal LCs are reprogrammed by selected cytokines known to be produced by keratinocytes under pathological conditions. (c) 2006 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.