Involvement of cytokines in the skin-to-lymph node trafficking of cells ofthe monocyte-macrophage lineage expressing a C-type lectin

The mechanism by which dermal cells expressing a macrophage calcium-type le ctin (MGL) trafficked to regional lymph nodes was investigated, Conditioned medium prepared from organ cultures of mouse skin sensitized with a mixtur e 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-1 beta, while addition of recombina nt IL-1 beta to the medium in which untreated skin was cultured induced los s of MGL(+) cells, Intradermal injection of recombinant IL-1 beta also resu lted in a transient increase of MGL(+) cells in the T cell area of draining lymph nodes in vivo, indicating that IL-1 beta is central in the entire pr ocess of MGL(+) cell trafficking to the lymph nodes. Supporting this is tha t cells producing IL-1 beta were detected in the epidermis of cultured skin even early after sensitization. The possibility that IL-1 beta simply down -regulates MGL expression was eliminated by Western blotting experiments wi th isolated MGL(+) cells treated with or without IL-1 beta, IL-1 alpha 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-1 beta, and antibodie s against them abrogated this, Isolated MGL(+) cells from skin cultured in type I collagen matrix in vitro displayed morphological changes upon exposu re to IL-1 beta, IL-1 alpha or TNF-alpha, indicating that these cytokines e xert a direct effect on these cells. Thus, pro-inflammatory cytokines, part icularly IL-1 beta, 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.