Tissue resident memory T cells; Mast cells; chronic contact hypersensitivity
570 Biowissenschaften; Biologie
Allergic contact dermatitis (ACD) is a T cell-mediated chronic inflammatory skin condition. ACD is one of the most common occupational diseases worldwide and causes severe quality of life impairment. Mast cells (MCs) are key players in chronic inflammation and involved in the regulation of immune homeostasis and immunosurveillance in various tissues including the skin. As of now, the role of MCs in the chronification of ACD is poorly understood. To address this, we induced chronic contact hypersensitivity (CCHS) to oxazolone (OXA), a contact allergen, in mice as a model for human ACD. Using different murine models, we investigated the role of MCs in CCHS. Mice deficient for MCs or treated with the MC inhibitor cromolyn developed exacerbated CCHS reactions and the reconstitution of MCs in MC-deficient mice prevented this. This exacerbation of inflammation and the protective effects of MCs in CCHS were both restricted to skin sites that had previously been exposed to the allergen, suggesting that MCs control CCHS inflammatory reactions by effects in local skin T cell populations. In support of this, skin areas pre-exposed to allergen showed more tissue resident memory (TRM) CD8β+ T cells in MC-deficient mice. These T cells were found to produce the cytokine interferon gamma (IFNɣ), and this pro-inflammatory cytokine was increased in the inflamed skin during CCHS responses in MC-deficient mice. The reduction of TRM CD8β+ T cells in MC-deficient mice prevented the exacerbation of inflammatory CCHS responses.
In conclusion, these findings demonstrate that MCs protect from exacerbated inflammatory responses in CCHS by controlling the accumulation of local cutaneous TRM CD8β+ T cell populations.
Falls Ihr Browser eine Datei nicht öffnen kann, die Datei zuerst herunterladen und dann öffnen.