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-1β, while addition of recombinant IL-1β to the medium in which untreated skin was cultured induced loss of MGL+ cells. Intradermal injection of recombinant IL-1β also resulted in a transient increase of MGL+ cells in the T cell area of draining lymph nodes in vivo, indicating that IL-1β is central in the entire process of MGL+ cell trafficking to the lymph nodes. Supporting this is that cells producing IL-1β were detected in the epidermis of cultured skin even early after sensitization. The possibility that IL-1β simply down-regulates MGL expression was eliminated by Western blotting experiments with isolated MGL+ cells treated with or without IL-1β. IL-1α and tumor necrosis factor (TNF)-α were also able to induce migration of MGL+ cells in the ex vivo assay in a manner akin to IL-1β, 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-1β, IL-1α or TNF-α, indicating that these cytokines exert a direct effect on these cells. Thus, pro-inflammatory cytokines, particularly IL-1β, 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.