International Immunology, Vol. 12, No. 12, 1695-1703,
December 2000
© 2000 Japanese Society for Immunology
Involvement of cytokines in the skin-to-lymph node trafficking of cells of the monocyte–macrophage lineage expressing a C-type lectin
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
1 Department of Microbiology, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka 422-8526, Japan
Correspondence to: T. Irimura
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-1
and tumor necrosis factor (TNF)- 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-1 or TNF-, 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.
Keywords: cell trafficking, delayed-type hypersensitivity, IL-1, skin sensitization
Transmitting editor: M. Miyasaka
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