Atopic dermatitis induces the expansion of thymus‐derived regulatory T cells exhibiting a Th2‐like phenotype in mice

Atopic dermatitis (AD) is a widespread inflammatory skin disease with an early onset, characterized by pruritus, eczematous lesions and skin dryness. This chronic relapsing disease is believed to be primarily a result of a defective epidermal barrier function associated with genetic susceptibility, immune hyper‐responsiveness of the skin and environmental factors. Although the important role of abnormal immune reactivity in the pathogenesis of AD is widely accepted, the role of regulatory T cells (T(regs)) remains elusive. We found that the T(reg) population is expanded in a mouse model of AD, i.e. mice topically treated with vitamin D3 (VitD). Moreover, mice with AD‐like symptoms exhibit increased inducible T‐cell costimulator (ICOS)‐, cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4)‐ and Glycoprotein‐A repetitions predominant receptor (GARP)‐expressing T(regs) in skin‐draining lymph nodes. Importantly, the differentiation of T(regs) into thymus‐derived T(regs) is favoured in our mouse model of AD. Emigrated skin‐derived dendritic cells are required for T(reg) induction and Langerhans cells are responsible for the biased expansion of thymus‐derived T(regs). Intriguingly, thymus‐derived T(regs) isolated from mice with AD‐like symptoms exhibit a Th2 cytokine profile. Thus, AD might favour the expansion of pathogenic T(regs) able to produce Th2 cytokines and to promote the disease instead of alleviating symptoms.