title: Involvement of cytokines in the skin-to-lymph node trafficking of cells of the monocyte-macrophage lineage expressing a C-type lectin.
abstract: The mechanism by which dermal cells expressing a macrophage calcium-type lectin (MGL) trafficked to regional lymph nodes was investigated. Conditioned medium prepared from organ cultures of mouse skin sensitized with a mixture of acetone and dibutylphthalate was shown to decrease the number of MGL(+) cells in the dermis in ex vivo organ culture assays. In in vitro culture of sensitized skin, the loss of MGL(+) cells was abrogated by the addition to the culture medium of mAb against IL-1ss, while addition of recombinant IL-1ss to the medium in which untreated skin was cultured induced loss of MGL(+) cells. Intradermal injection of recombinant IL-1ss also resulted in a transient increase of MGL(+) cells in the T cell area of draining lymph nodes in vivo, indicating that IL-1ss is central in the entire process of MGL(+) cell trafficking to the lymph nodes. Supporting this is that cells producing IL-1ss were detected in the epidermis of cultured skin even early after sensitization. The possibility that IL-1ss simply down-regulates MGL expression was eliminated by Western blotting experiments with isolated MGL(+) cells treated with or without IL-1ss. IL-1alpha and tumor necrosis factor (TNF)-alpha were also able to induce migration of MGL(+) cells in the ex vivo assay in a manner akin to IL-1ss, and antibodies against them abrogated this. Isolated MGL(+) cells from skin cultured in type I collagen matrix in vitro displayed morphological changes upon exposure to IL-1ss, IL-1alpha or TNF-alpha, indicating that these cytokines exert a direct effect on these cells. Thus, pro-inflammatory cytokines, particularly IL-1ss, are produced at the site of skin sensitization and are involved in at least initiating the trafficking of cells expressing MGL to the lymph nodes.
authors: Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: K H
authors: KH
authors: Chun
authors: Y
authors: Y
authors: Imai
authors: N
authors: N
authors: Higashi
authors: T
authors: T
authors: Irimura
mesh_terms: D000096:Acetone / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D003993:Dibutyl Phthalate / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D007114:Immunization; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000096:biosynthesis / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology; D037102:Lectins / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D009924:Organ Culture Techniques; D012867:Skin / Q000187:drug effects / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D016898:Interferon-alpha; D007375:Interleukin-1; D037102:Lectins; D000096:Acetone; D003993:Dibutyl Phthalate