Abstract
Allergic contact dermatitis (ACD) is a frequent inflammatory skin disease that evolves upon exposure to contact allergens in sensitized individuals. Both the adaptive and innate immune system play pivotal roles in the pathogenesis of ACD. While the importance of T cells is undisputed, the relevance of B lymphocytes is less clear. The published data support a critical role for NFATc1 in B cell activation. Therefore, we investigated the impact of NFATc1 on B cell function during murine contact hypersensitivity (CHS), the mouse model for human ACD. Compared with wild-type mice, B cell-specific ablation of NFATc1 (Nfatc1f/f x mb1-cre) resulted in significantly diminished CHS responses measured by ear thickness (0.81 ± 0.02 mm vs. 0.48 ± 0.02 mm (p = 0.0007)) to the obligate contact allergen 2,4,6-trinitrochlorobenzene, accompanied by a marked increase in the frequency of IL-10-producing regulatory B cells. Flow cytometric analysis showed that IL-4- and IL-17-producing CD4+ T cells were reduced, while IFN-γ-producing CD4+ T cells were marginally increased in Nfatc1f/f x mb1-cre mice. In conclusion, NFATc1 mediates CHS responses by modulating the development of IL-10-producing B cells. These findings support the compelling notion that targeting NFATc1 may represent a potential therapeutic strategy for allergic responses.