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

SummaryBackgroundTo understand the behavioral biology of Langerhans cells (LCs), we recently recorded time-lapse images of LCs in the knock-in mice expressing the I-Aβ 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.ObjectiveTo define underlying mechanisms by which hapten treatment alters LC behaviors.MethodsThe I-Aβ-EGFP mice received subcutaneous (s.c.) injection of recombinant IL-1α or TNFα (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-1Ra) or soluble TNF receptor-2 (sTNFR2) (0.5 μg/animal) was s.c. injected into the ear skin 30 min before topical application of DNFB, and LC behaviors analyzed 30 h later.ResultsLocal injection of IL-1α or TNFα induced significant, albeit modest, augmentation of both dSEARCH and lateral migration. Co-injection of TNFα and IL-1α 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.ConclusionIL-1 and TNFα 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.