title: Lymphatic dysfunction impairs antigen-specific immunization, but augments tissue swelling following contact with allergens.
abstract: The lymph transports tissue-resident dendritic cells (DCs) to regional lymph nodes (LNs), having important roles in immune function. The biological effects on tissue inflammation following lymphatic flow obstruction in vivo, however, are not fully known. In this study, we investigated the role of the lymphatic system in contact hypersensitivity (CHS) responses using k-cyclin transgenic (kCYC(+/-)) mice, which demonstrate severe lymphatic dysfunction. kCYC(+/-) mice showed enhanced ear swelling to both DNFB and FITC, as well as stronger irritant responses to croton oil compared with wild-type littermates. Consistently, challenged ears of kCYC(+/-) mice exhibited massive infiltrates of inflammatory cells. In contrast, DC migration to regional LNs, drainage of cell-free antigen to LNs, antigen-specific IFN-γ production, and lymphocyte proliferation were impaired during the sensitization phase of CHS in kCYC(+/-) mice. Transfer experiments using lymphocytes from sensitized mice and real-time PCR analysis of cytokine expression using challenged ear revealed that ear swelling was enhanced because of impaired lymphatic flow. Collectively, we conclude that insufficient lymphatic drainage augments apparent inflammation to topically applied allergens and irritants. The findings add insight into the clinical problem of allergic and irritant contact dermatitis that commonly occurs in humans with peripheral edema of the lower legs.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. sugayam-der@h.u-tokyo.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kuwano
authors.forename: Hiraku
authors.initials: H
authors.lastname: Suga
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyagaki
authors.forename: Hanako
authors.initials: H
authors.lastname: Ohmatsu
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okochi
authors.forename: Andrew
authors.initials: A
authors.lastname: Blauvelt
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003436:Croton Oil / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000276:immunology / Q000494:pharmacology; D004487:Edema / Q000276:immunology; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D007114:Immunization / Q000009:adverse effects*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007509:Irritants / Q000276:immunology / Q000494:pharmacology; D008208:Lymphatic System / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008222:Lymphokines; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D000485:Allergens; D016207:Cytokines; D007509:Irritants; D008222:Lymphokines; C057264:antigen-specific helper factors; D003436:Croton Oil; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene; D016650:Fluorescein-5-isothiocyanate