Early molecular events in the induction phase of contact sensitivity.

Abstract

To assess changes in epidermis-derived cytokine mRNA levels early in the afferent phase of allergic contact sensitivity, total epidermal mRNA was analyzed at various times after painting skin with haptens. We used a sensitive reverse transcriptas-polymerase chain reaction technique to quantitatively compare the regulation patterns of the following mRNAs: class H major histocompatibility complex I-Aa, tumor necrosis factor a (TNF-a), interleukin (IL) la, IL-1l, interferon (IFN) y, granulocyte/macrophageoolonystimulaing factor, IFN-induced protein 10, and marh inflammatory protein 2. Enhanced Langerhans cell-derived IL-13 mRNA signals were detected as early as 15 min after skin painting with allergens. TNF-a, IFN-y, and granulocyte! macrophage colony-stimulating factor mRNAs were found to be upregulated after application of allergens, irritant, and tolerogens, but class H major histocompatibility complex I-Aa, IL-la, IL-ljJ, IFN-induced protein 10, and macrophage infammatory protein 2 mRNAs were upregulated only after allergen painting. Depletion of specific cell populations demonstrated that Langerhans cells were the primary source of the IL-1u and class II major histocompatibility complex I-Aa mRNAs, keratinocytes were the primary source of TNF-a, IL-Ia, IFN-induced protein 10, and macrophage inlammatory protein 2, and infiltrating T lymphocytes were the source of lFN-y. Relevance of the molecular was Wasdemonstrated by the identification of biologically active IL-la and im oreactive TNFI-a in culture supernatants. These studies demonstrate that Langerhans cell-derived and certain keratinocytederived cytokine mRNAs are selectively upregulated by allergens in the very early afferent phase of contact sensitivity.

Migration of Langerhans cells and dermal dendritic cells in skin organ cultures: augmentation by TNF-α and IL-1 β

“…Our data confirm and extend data recently reported by others [16,17,36,37] in that this study specifically deals with cutaneous aspects of migration: first, we observe a dose-dependent differential effect of TNF-␣ on DC migration (enhancement by low doses/ inhibition by high doses). Second, we extend the description of cytokine influence on migration to the dermal compartment (effect of cytokines on migration within dermal lymphatics).…”

“…There, the cytokines are not accessible to measurement by ELISA. In the model of murine contact hypersensitivity it has been shown that mRNA for both cytokines is expressed in the epidermis on application of a contact sensitizer and concomitant with the emigration of Langerhans cells from the epidermis [37]. The same was found in a murine model of heart transplantation [43], where DCs also migrate out of the organ [44].…”

Identification of a Novel, Dendritic Cell-associated Molecule, Dectin-1, by Subtractive cDNA Cloning

“…With respect to the source of dectin-1 mRNA expression, depletion of the Ia ϩ epidermal cell population (i.e. Langerhans cells) abrogated almost completely dectin-1 mRNA, as well as IL-1␤ mRNA, which is known to be expressed exclusively by Langerhans cells in murine epidermis (18,55,56). This corroborates our observations that dectin-1 mRNA was detected by Northern blotting in the XS52 Langerhans cell-like line, but not in cell lines derived from other epidermal cell populations, i.e.…”

Mice deficient in IL-1beta manifest impaired contact hypersensitivity to trinitrochlorobenzone.

“…An additional selective role for IL-1[3 has been proposed in the development of contact hypersensitivity responses in the skin (25,26). Contact sensitizers increase the levels of mRNA for several cytokines in the skin, including IL-lct, IL-113, and TNFcx.…”