Altered Permeability and Disordered Cutaneous Immunoregulatory Function in Mice with Acute Barrier Disruption

Abstract

In vivo and in vitro T-cell-activating ability of murine epidermal cells (EC) was investigated in acutely barrier-disrupted skin by extraction of epidermal lipids with acetone or removal of corneocytes by tape stripping. Contact sensitivity (CS) to 2,4-dinitrofluorobenzene (DNFB) and picryl chloride (PCl) and contact photosensitivity (CPS) to tetrachlorosalicylanilide (TCSA) were significantly augmented when challenged or sensitized at sites treated with acetone 24 h before, compared with the intact skin. CS to DNFB was also enhanced by tape stripping, but not by water rubbing, suggesting that physical stress or a toxic effect of acetone was not responsible for the augmentation. Semi-quantification of TCSA-EC photoadducts showed markedly increased permeability of hapten in the epidermis 24 h after acetone treatment. Bioactive IL-1alpha was more pronounced in barrier-disrupted than in intact skin. Lymph node T cells from PCl-sensitized mice proliferated significantly more in a hapten-specific and co-stimulatory molecule-dependent manner in response to trinitrophenylated (TNP) EC from acetone-treated skin than to those from untreated skin. Immunofluorescence staining of epidermal sheets and flow cytometric analysis of dispersed EC showed that subpopulations of Langerhans cells (LC) in acetone-rubbed or tape-stripped skin expressed major histocompatibility complex class II CD54 and CD86 molecules at levels higher than the rest of LC and LC from water-treated or untreated epidermis. Therefore, not only increased permeability of hapten through the epidermis but also altered immune functions of EC potentiate T-cell activation in acute barrier disruption. Such augmentation of immune reactivity may be critical to elimination of environmental noxious agents that penetrate easily into the barrier-disrupted epidermis.

Application of Microneedles to Skin Induces Activation of Epidermal Langerhans Cells and Dermal Dendritic Cells in Mice

“…28,29) After TS treatment, the RMFI values for MHC class II, CD86, CD80, and CD54 on LCs were 1.94±0.27, 1.66±0.25, 1.17±0.10, and 1.26±0.10, respectively, and the degree of expression of MHC class II and CD86 tended to be higher than those of the control group. This result was consistent with the findings of Seo et al 29) and Nishijima et al, 30) suggesting the relevance of TS treatment as a positive control. To compare the effect of insertion depth of microneedles on the skin, different needle sizes (500 or 300 µm) were used.…”

“…Tokura et al demonstrated that epidermal LCs activated by TS treatment migrated to the peripheral draining lymph nodes at 24-48 h after treatment. 30) Thus, this may explain the observed decrease in MHC class II staining at 24 h in our study demonstrated after TS treatment.…”

“…30,39) That is, innate immune activation involving a costimulatory signal is essential and important for subsequent acquired immunity. The best-characterized T cell/APC interactions at the molecular level include CD4/MHC class II, CD28/B7 (CD86, CD80), and LFA-a/CD54.…”

“…Strong antigen-presenting capacity was obtained in activated LCs isolated from tape-stripped (TS) skin compared with LCs isolated from nonactivated intact skin. 29,30) These findings suggest that physical stimulation such as TS of the skin provide a possible beneficial effect for the enhancement of antigen-presenting capacity.…”

Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

“…[8][9][10] TS leads to removal of the outermost horny layer of the skin, resulting in enhanced permeability and maturation and activation of LCs via inflammatory cytokines secreted from keratinocytes. 11,12 The barrier function of the SC can also be bypassed by hydration of the skin, which leads to swelling of the keratinocytes and pooling of fluid into intercellular spaces. This kind of pretreatment of the skin leads to development of humoral 13,14 and Th responses after TCI with proteins or peptides.…”