title: Enhanced epidermal Langerhans cell migration in IL-10 knockout mice.
abstract: The migration of epidermal Langerhans cells (LC) to lymph nodes (LN) is critical in the initiation of contact hypersensitivity (CHS) responses. Studies suggest that contact allergen-induced epidermal proinflammatory cytokines, including IL-1 and TNF-alpha, play important roles in promoting LC migration. Contact allergens also induce epidermal anti-inflammatory cytokines such as IL-10. Since IL-10 down-regulates proinflammatory cytokine production and inhibits CHS, we hypothesized that IL-10 might inhibit LC migration. To test this hypothesis, IL-10 knockout (KO) mice were epicutaneously sensitized with the hapten, FITC, and 24 h later hapten-bearing cells in the draining LN were examined. The number of hapten-bearing cells in the LN was significantly greater in IL-10 KO mice than in wild-type mice. The mutant mice also had an exaggerated CHS to FITC. Pretreatment with anti-TNF-alpha Ab or IL-1R antagonist significantly reduced the number of hapten-bearing cells in the LN, suggesting that IL-10 modulation of LC migration involves IL-1 and TNF-alpha. Moreover, IL-10 KO mice demonstrated a greater increase in TNF-alpha, IL-1alpha, and IL-1beta mRNAs in the allergen-exposed epidermis, and keratinocytes derived from the mutant mice were able to produce higher amounts of TNF-alpha and IL-1alpha protein. These data suggest that IL-10 plays an inhibitory role in LC migration and that this effect may occur via the down-regulation of TNF-alpha and IL-1 production.
authors.affiliation: Division of Dermatology, Sunnybrook Health Science Center, University of Toronto, Ontario, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Zhuang
authors.forename: H
authors.initials: H
authors.lastname: Fujisawa
authors.forename: G A
authors.initials: GA
authors.lastname: Shinder
authors.forename: C
authors.initials: C
authors.lastname: Feliciani
authors.forename: G M
authors.initials: GM
authors.lastname: Shivji
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: P
authors.initials: P
authors.lastname: Amerio
authors.forename: P
authors.initials: P
authors.lastname: Toto
authors.forename: D N
authors.initials: DN
authors.lastname: Sauder
mesh_terms: D000818:Animals; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000378:metabolism; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007106:Immune Sera / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics* / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D006241:Haptens; C507764:Il1rn protein, mouse; D007106:Immune Sera; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016650:Fluorescein-5-isothiocyanate