Type 2 immunity plays an essential role for murine model of allergic contact dermatitis with mixed type 1/type 2 immune response

Abstract

Background: Both human and mouse allergic contact dermatitis (ACD) frequently demonstrates a combined type 1 and type 2 immune response. However, the relative importance of type 2 immunity in this setting has been incompletely understood yet. Objective: To explore an effector function of type 2 immunity in ACD with mixed type 1/type 2 immune re-sponse. Methods: Gene expression characteristics of contact hypersensitivity (CHS) model was examined by quantitative polymerase chain reaction. Cytokine profile of T cells was analyzed by flow cytometry. The involvement of type 2 immunity was assessed by antibody-mediated cytokine neutralization and cell de-pletion. The role of specific subset of cutaneous dendritic cells was evaluated using diphtheria toxin-in-duced cell-depleting mouse strains. Results: Oxazolone-induced CHS revealed a combination of type 1/type 2 gene expression. The severity of oxazolone-induced CHS was ameliorated by neutralization of IL-4 but not of IFN-gamma, indicating that type 2 immunity plays a dominant effector function in this mixed type 1/type 2 model. Mechanistically, type 2 effector immunity was mounted by CD301b+Langeirn- dermal dendritic cells in part through thymic stromal lymphopoietin-interleukin 7 receptor alpha signaling-dependent manner. Conclusion: Our findings suggest the clinical rationale for targeting type 2 immunity as a relevant ther-apeutic strategy for the mixed immune phenotype of ACD.