Roles for IL-1 and TNFalpha 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-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.


CONCLUSIONS
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.
Nishibu
Akiko
A
Department of Dermatology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Ward
Brant R
BR
Boes
Marianne
M
Takashima
Akira
A
D000287:Administration, Topical; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004139:Dinitrofluorobenzene / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D006241:Haptens / Q000008:administration & dosage* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D007279:Injections, Subcutaneous; D053582:Interleukin-1alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D007801:Langerhans Cells / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D005456:Fluorescent Dyes; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D053582:Interleukin-1alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004139:Dinitrofluorobenzene