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

J Dermatol Sci. 2007 Jan;45(1):23-30. doi: 10.1016/j.jdermsci.2006.10.003. Epub 2006 Nov 22.

Abstract

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-Abeta 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-Abeta-EGFP mice received subcutaneous (s.c.) injection of recombinant IL-1alpha or TNFalpha (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 microg/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-1alpha or TNFalpha induced significant, albeit modest, augmentation of both dSEARCH and lateral migration. Co-injection of TNFalpha and IL-1alpha 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 TNFalpha 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Topical
  • Animals
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Dinitrofluorobenzene / antagonists & inhibitors
  • Dinitrofluorobenzene / pharmacology
  • Drug Synergism
  • Fluorescent Dyes
  • Green Fluorescent Proteins
  • Haptens / administration & dosage*
  • Haptens / pharmacology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Injections, Subcutaneous
  • Interleukin-1alpha / administration & dosage
  • Interleukin-1alpha / antagonists & inhibitors
  • Interleukin-1alpha / pharmacology
  • Interleukin-1alpha / physiology*
  • Kinetics
  • Langerhans Cells / drug effects*
  • Langerhans Cells / physiology*
  • Mice
  • Mice, Transgenic
  • Recombinant Proteins / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Fluorescent Dyes
  • Haptens
  • Histocompatibility Antigens Class II
  • Interleukin-1alpha
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Dinitrofluorobenzene